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Researchers have discovered the first genetic mutation associated with hypertrophic cardiomyopathy and sudden death in golden retrievers.
The work could lead to increased early detection and disease prevention for the breed while further shaping our understanding of the disease in humans.
Hypertrophic cardiomyopathy (HCM) is a cardiac disease that most commonly affects humans and cats but was previously considered rare in dogs. In HCM, the left ventricular muscle thickens, affecting the heart’s ability to deliver oxygenated blood to the body. The disease can lead to abnormal blood clotting, irregular heart rhythms, and heart failure, although in up to 50% of cases individuals with the disorder show no clinical signs.
HCM affects approximately one in 500 humans and one in seven cats, representing one of the top causes of sudden death in both populations.
In the study, the research team looked at the whole genome sequences for three related golden retriever puppies less than two years of age who all suffered sudden cardiac deaths. Genetic sequences were compared to other dogs within the puppies’ family tree, sequences from over 2,500 unrelated dogs of various breeds, and sequences from wolves and coyotes.
Bioinformatic analysis and sequential filter steps led the team to identify a single genetic variant located in a gene called Cardiac Troponin-I, or TNNI3.
“In humans, TNNI3 mutations are associated with juvenile HCM and sudden death,” says Victor Rivas, DVM student and PhD graduate at North Carolina State University.
“This is the first genetic variant to explain HCM outside of humans and cats. And while it is specific to golden retrievers, it’s the first variant to be described in any dog breed.” Rivas is first author of the study.
The researchers also found that the mutation is autosomal recessive, which means that two copies of the gene—one from each parent—must be present for the disease to occur. In the case of the affected puppies, both parents were cardiovascularly normal, but each carried a copy of the mutation.
The researchers hope that this information can be used to prevent the spread of the TNNI3 variant—and thereby HCM—through the breed. Golden retriever owners who may be interested in breeding can have genotype testing performed for this mutation to determine whether their animal is a carrier.
“The positive news is that by collaborating with the golden retriever community we may be able to ensure that HCM remains a very rare disease in dogs,” Rivas says.
“Additionally, the case similarities in humans and golden retrievers with these TNNI3 variants is remarkable and could lead to translational health studies that can shape our understanding of the disease mechanisms and ultimately benefit humans with similar mutations.”
The study appears in Circulation: Genomic and Precision Medicine.
Additional contributors are from NC State, the University of Calgary, Pulse Veterinary Cardiology, and Highview Animal Clinic.
Aziz Ansari’s feature directing debut, “Good Fortune,” wasn’t meant to be his first effort as a filmmaker: That would’ve been “Being Mortal,” called off mid-shoot in 2022 amid accusations of misconduct against Bill Murray. So it was inevitable that alongside the TIFF premiere of “Good Fortune,” a comedy starring Keanu Reeves and “Being Mortal” star Seth Rogen, he’d have to address the canceled film. And it turns out, they share thematic DNA.
The South Carolina-born Indian-American actor, writer, director, and stand-up comedian is known by audiences worldwide as serial entrepreneur Tom “Treat Yo Self” Haverford on NBC’s “Parks and Recreation,” and as the more somber, lovelorn Dev Shah on the Netflix hit series “Master of None.”
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Could “Good Fortune” and his should-have-been debut “Being Mortal” have swapped titles? After all, in the TIFF premiere, Keanu Reeves plays Gabriel, the Angel of Texting and Driving — in L.A., yes, the City of Angels, where in this comedy, angels exist — and finds himself demoted to human by his angel boss (Sandra Oh). Thus, he becomes mortal. “Whoa!” Ansari told IndieWire in Toronto. “I gotta process that,” when asked.
When the news of “Being Mortal’s” cancellation broke in April 2022, Ansari said he got a deluge of “I’m sooo sorry” texts. He recalled thinking, “I can’t deal with this. I don’t wanna be in this woe-is-me moment.” Ansari said he then called Seth Rogen, also a star of “Being Mortal.” He told Rogen, “Hey, I know you’re free and were supposed to work today. If you wanna make this day less shitty for me, can you read this script [for ‘Good Fortune’]? He said, yeah, and he called me in two hours and said, ‘I’m in, let’s do it.’”
That’s how “Good Fortune” began. Ansari had a basic version of the story ready, where he plays Arj, a down-on-his-luck documentary film editor living out of his car and forced to participate in the gig economy as a Taskrabbiter and home-improvement store worker. Through the latter, Arj meets a union organizer (Keke Palmer, also a “Being Mortal” star), whom he begins dating. Through the former, Arj meets Jeff (Seth Rogen), a venture-capitalist angel investor in tech companies. When Gabriel (Reeves) intervenes because he can’t help but take pity on Arj’s lost soul, Gabriel decides to swap Arj and Jeff’s lives. There you have it, a “Prince and the Pauper”-esque fable, touched by an angel, with a rebellious and playful streak of working-class consciousness.
Empathy for the working class indeed feels like a far cry from Tom Haverford and Dev Shah. When asked about shifting from narratives about the middle class — Ansari co-created “Master of None” with his longtime collaborator Alan Yang, also a producer on “Good Fortune” — and from TV to film, Ansari said, “’Master of None’ was almost the perfect training ground to get ready to do this film. There was an episode on Season 2 called ‘New York, I Love You’ and another episode in Season 3, where the character played by Naomi Ackie [goes] through IVF. For both of those episodes, I had to do a lot of work interviewing people, trying to understand experiences that were not my own… I hope for people [who] like ‘Master of None,’ [that] this is kind of what they hoped I would do with a movie. It has a lot of the same DNA as ‘Master.’ It’s about seeing things from other people’s perspectives.”
Anasri said, “So for ‘New York, I Love You,’ there was a segment about a cab driver, a doorman, and a woman who was Deaf. This guy Stefano and I did a DoorDash ride-along, and then I took over his account and did stuff for a day. That fueled the whole segment with Seth [in ‘Good Fortune’], where he ends up doing DoorDash. I also spoke with this guy, Vincent, who tried to unionize a Home Depot in Philadelphia. He was so inspiring. The Elena character that Keke Palmer plays [is based on him]. So we interviewed a lot of people that did those kinds of gigs. That process is something that helped me tremendously in doing ‘Good Fortune.’”
Ansari said the script’s conceit about angels really began to hit home once he pulled off a casting coup with Keanu Reeves. That Ansari is himself an actor and a stand-up comedian helped him figure out the comedy of “Good Fortune,” plus the fact that he was back in the familiar mode of acting and directing in equal measure, as he had in “Master of None.” (By contrast, in “Being Mortal,” Ansari said he had a much smaller role.)
“’Being Mortal’ is based on a book by Atul Gawande that’s about life (and death) issues,” said Ansari. “It was pretty heavy at times, and it was a heavy shoot. So I was excited to do something that was much more straightforward comedy. When Keanu’s name first came up, I started watching all his films like ‘Point Break’ and ‘Speed,’ but I went back to the comedies he had done, like ‘Bill and Ted’s Excellent Adventure’ and ‘Parenthood’ in particular. You kind of see little bits of his comedy power. He’s very funny when he’s playing a guy that’s kind of naive, but at the same time so sweet. And that’s Gabriel, right? He’s so lovable. But he’s kind of dumb. [Laughs]“
In thinking about Reeves while looking at the script, Ansari said he could “just imagine him having this bright-eyed wonder about the internet, him being this angel that gets thrown into the deep end of being a human and struggling in L.A., but having the attitude he does. I just had a feeling it would work… He’s so great, he’s the soul of the movie.”
How the dating scenes between Arj (Ansari) and Elena (Ackie) are blocked brings to mind “Master of None’s” approach to the same, and Ansari agreed. He said while planning to shoot those romantic moments for “Good Fortune” that he and Alan Yang recognized this is their “bread and butter.”
Ansari also edited the film while he shot, which is a bold choice. “This notion of watching the rough cut is a nightmare. You’re so scared. If you edit as you go along, you minimize that a little bit,” Ansari said. “You just start feeling the rhythms of the movie, and you start understanding what’s working camera-wise in terms of the cinematic language. ‘Oh, these kinds of shots feel good,’ or ‘oh, let’s stay in these singles a little bit longer.’ Whatever it is, you just learn what your movie is, [and] you can kind of lean into things.” Ansari credited his editor, Daniel Haworth, with whom he worked on “Master” as well. Whenever Haworth was on set, Ansari would run in to take a look at the dailies and the evolving cut.
“Master of None” fans will be delighted to see the director’s father (Shoukath Ansari) show up in special appearances, though Ansari’s mother (Fatima Ansari) doesn’t feature in “Good Fortune” as she did in that Netflix show. Ansari said that his mom hates acting, but it was a lot of fun having his dad around, because a lot of the story is about the need for family in a place like L.A.
Aziz Ansari as Arj and Keanu Reeves as Gabriel in ‘Good Fortune’Eddy Chen/Lionsgate
“Parks and Rec” fans will also notice Joe Mande, who played Morris for a few episodes on the NBC sitcom and served as a writer. In the film, Arj meets Joe’s character while Taskrabbiting in line at a Cinnabon. The casting of secondary and tertiary characters feels very intentional in this film, adding to the groundedness of a movie as much about Los Angeles as it is set there.
“We had an amazing cast director, Carmen Cuba. One role that was very fun to cast was Felipe [Felipe Garcia Martinez], who plays a dishwasher that Keanu works with,” Ansari said. “We’d been reading these people, and none of them really felt like the real guy that would be in the back of the kitchen with Keanu. So me and my producer Kelsey [Comeau] went down to his restaurant, and he came out, and we did some of the scenes.”
He added, “Then I called Keanu and said, ‘Hey, I have this idea for that character. Would it be cool if we used a real guy, because I think he would bring some authenticity to the role?’ He said, ‘Yeah, I’m down.’ So we use Felipe, and he shows up, and he’s the only person I met who doesn’t know who Keanu Reeves is! Months after we wrapped, I went down to the restaurant, and I was like, ‘Felipe!’ He was there. And I was like, ‘Did you tell all these people you’re a movie star now?’ And they’re like, ‘Oh yeah, he’s been telling us all the time. He’s telling us about Keanu and everything.’ Yeah, Felipe’s great.”
If Ansari were an angel, what would his department be? Ansari said, “Maybe the Angel of Screenwriting Inspiration? I love to help writers out that are stuck in the jam.”
“Good Fortune” premiered at the 2025 Toronto International Film Festival. Lionsgate will release the film in theaters on Friday, October 17.
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Allen Blickle, the original drummer for the Grammy-nominated sludge metal band Baroness, has died at the age of 42.
“It breaks my heart to have to share the news that my dear friend, creative partner and former bandmate Allen Blickle passed away a few days ago,” Baroness frontman John Baizley said in a statement. “I’m still in shock that he’s gone. We ask for understanding as his family and this band process his passing and grieve his loss. Allen, I love you and miss you. I treasure every moment we shared.”
Though the cause of death has not been revealed, Laura Pleasants, of the Georgia metal band Kylesa, wrote in her Instagram tribute that “we all thought you had this thing beat. Fuck, we were supposed to hang out when i got back from tour…Gone too soon my friend. I’m glad you are at peace and no longer in pain. Much love to you.”
Blickle co-founded Baroness in Savannah, Georgia in 2003, alongside Baizley, bassist Summer Welch, and guitarist Tim Loose. He released three albums with the band: their 2007 debut Red Album, 2009’s Blue Record, and 2012’s Yellow & Green.
Following the band’s tour bus crash in the U.K. in August 2012 — in which the vehicle plunged 30 feet off a viaduct near Bath, England, in heavy rain — Blickle was hospitalized for two weeks with fractured vertebrae. He left the band the following year, alongside bassist Matt Maggioni.
“The accident was much more to me than just a near-death experience,” Blickle told The Fader in 2013. “It made me rethink a lot in my life and has been the most difficult time I’ve been through thus far. It was a horrible memory, but I’m trying not to let it define me or stop me from doing what I love. Let it be and keep moving.”
He also spoke about his relationship with his bandmates following his departure. “After the accident, there was space put between us that I regret to say was mostly my fault,” he said. “I was in some way pushing myself in another direction. I didn’t know how to handle the horrible situation we all went through, but who does? It’s not easy and continues to be somewhat difficult. I do miss playing with them and I have relayed to them that when the time is right, I would like to be on the road again. It’s not up to me at this point. I just don’t want any resentment to build between any of us. We are old friends and have worked really hard together for years. Friends first — that’s the most important thing to remember.”
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Baroness has since released three more LPs (2015’s Purple, 2019’s Gold & Grey, and 2023’s Stone), while Blickle went on to work with bands like Romantic Dividends, A Place to Bury Strangers, and Alpaca. When Pharoah Sanders died in 2022, Blickle wrote on Instagram that he helped record an interview with the legendary saxophonist for The New Yorker.
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In recent years, Blickle worked in film and TV as a composer and in sound design, including Netflix’s 2020 series We Are the Champions and Best of Stand-Up (2020 and 2022).
“Follow your gut,” Blickle told The Fader. “Take chances. Make sure to keep your friends close, even if things come between you. The music business is not an easy industry and people turn their backs on you really fast.”
COVID vaccines may be hard to find this season. Credit: Adobe Stock
COVID-19’s grip may have loosened, but its effects on pregnancies linger in data showing higher preterm birth risks for infected mothers. A new analysis from Panalgo, a Norstella company, presented at ICPE 2025, used linked U.S. claims data to match COVID-positive pregnant women against controls. The data revealed a statistically significant increase in preterm deliveries; lower rates of low birth weight were observed, with significance not specified.
More data will be needed to interpret the findings amid conflicting prior studies. “This was a starting point for looking at more longer-term impacts of a mother’s COVID-19 infection on the outcome of their children,” said Mike Munsell, Ph.D., director of real-world data and HEOR at Panalgo. He noted a rise in preterm births among infected mothers and, counterintuitively, lower rates of low birth weight, signals the team plans to track as the “children of the COVID era” move through early milestones.
Digging into the COVID-19 pregnancy data
Mike Munsell, Ph.D.
The ICPE 2025 poster, “The Effect of COVID-19 During Pregnancy on Fetal Outcomes: A Propensity Score-matched Analysis Using Mother-infant Linked Claims Data,” taps Norstella’s mother-infant linkage to examine how infection during pregnancy relates to delivery outcomes in the real world. The team matched mothers with a documented COVID-19 infection during pregnancy to contemporaneous mothers without recorded infection and controlled for the number of vaccinations and other relevant factors.
“At Norstella, we have very large datasets that we can link at the patient level,” said Munsell. “One of the ones that we have links mothers to their infants, and you can connect the characteristics of the mother with the outcomes of the infant.”
The core signal is straightforward on one dimension and puzzling on another. “Mothers who had COVID-19 during pregnancy were more likely to have a preterm birth, which was statistically significant compared to controls,” Munsell said.
At the same time, he noted lower rates of low birth weight among infants born to infected mothers. “That one’s a little bit of a puzzle,” he said. The literature varies, and the team plans to incorporate additional covariates. “There’s a lot of noise in this type of data,” he said, pointing to the need to broaden socio-demographic information to better understand fetal outcomes. “There’s a lot of value in being clear on the limitations of your data and the population you are studying. If you can be as clear and upfront about what you’re studying, that’s probably more practical and beneficial than being as general as possible.”
The children of the COVID era
Methodologically, the analysis relied on structured administrative claims and enrollment files to maximize completeness and establish clear timelines. “This one used structured claims data. We had enrollment files, which are particularly helpful for understanding the timeline for pregnancy,” Munsell said. “We identify the point in time when a child is born and link that with the mother’s record, and then approximate when the start of pregnancy was.” The same ecosystem allows deeper dives when needed. “We do have the ability within our dataset to tokenize more data and bring in a smaller sample with overlapping EMR and clinical notes and some of the text fields,” he said. He put the mother-infant linkage at “close to around 3 million mother-infant pairs,” drawn from “close to 170 million covered lives.”
Beyond the immediate results, Munsell presented the work as a starting point. “We’re at an interesting phase now. The pandemic has subsided, but a lot of work is happening on the ‘children of the COVID era.’ I have one as well; they’re entering kindergarten this year,” he said. “We would like to follow these infants further in the dataset” to clarify mechanisms behind the preterm-birth signal and to test whether the low-birth-weight finding persists after incorporating broader social and clinical factors.
The other ICPE poster: ES-SCLC in the real world
Munsell’s team also presented on extensive-stage small cell lung cancer (ES-SCLC ), analyzing U.S. treatment patterns, resource use, and outcomes. “Yes. That one also used administrative claims data,” he said. “Extensive stage is fairly aggressive, but there have been a lot of developments in treatment in the last five years, specifically immune checkpoint inhibitors becoming a first-line therapy along with chemotherapy.”
“Part of our work was looking at the rate for which, within this fairly recent dataset, you’re seeing patients receiving both of those as a first-line treatment,” Munsell said. “Close to 40% of our population had these newer treatments as a first-line therapy along with their chemotherapy. That was reassuring, to see that shortly after the approval and recommendation, patients were using those treatments.”
Despite uptake, burden remained high. “We’re still seeing close to two-thirds of patients having brain metastases at a certain point and over a third having a secondary primary malignancy, even with these new treatments,” he said. “So, this was mostly a study looking at the landscape of treatments available to these patients, but also still highlighting that the burden of illness is still pretty high.”
“One newer area that is just recently being looked at for these patients is radiation therapy happening further down the lines of treatment,” Munsell said. “We saw a smaller subset, about 15% of our patients, also receiving radiation therapy.” He added, “There was a recent sub-analysis from a clinical trial that referenced that, potentially, what they’re seeing in men is a potential increase in overall survival with radiation therapy. I don’t know the full mechanisms for why that is, and they’re still trying to confirm that. So we looked into whether we see a high proportion of men receiving radiation therapy. At this point in the data, it’s fairly equal among men and women receiving that treatment.”
“For this one, we also have the ability to link in mortality data,” Munsell said. “The hope with this cohort that we first highlighted was to confirm that the burden of illness is still relatively high, confirm that these new treatments are being used, and also confirm that there are still pretty severe outcomes. We can then follow these patients over time and do overall survival analysis, but the hope is also to pull in clinical notes to get a better description around disease staging at the time of index, which really impacts overall survival.” For now, he added, “We’re kind of going based on diagnosis codes right now, and treatment being indicative of the type of disease, which is a good starting point. But pulling in unstructured clinical notes, particularly for oncology, goes a really far way, because each of these patients has a very unique and individualized disease.”
Filed Under: clinical trials, Drug Discovery, Infectious Disease, machine learning and AI Tagged With: cancer treatment gaps, clinical research, covid-19, drug discovery, lung cancer, Maternal health, neonatal outcomes, obstetrics, oncology, pregnancy risks, preterm birth, real-world data
Late at night, after an exhausting hike up Indonesia’s Mount Gede, Maya wakes to find her friend Itha missing from their tent. Several minutes of frantic searching later, she finds her crouched, alone, in a patch of tall grass – giggling.
“I’m talking to my friend,” Itha explains. Except no one else is there.
My whole body jolts as that “friend” suddenly erupts onto the screen. It’s the most terrified I’ve ever been in a movie theater – the kind of scared that has you peeking through your fingers and spilling popcorn on your neighbor. In my case, that’s longtime Indonesian film critic Ekky Imanjaya, who looks completely unfazed.
Why We Wrote This
Indonesia’s horror film boom points to deeper religious and cultural beliefs behind the scary movies that are packing cinemas.
He’s seen hundreds of movies like “Haunting of Mount Gede.” Horror is by far the most popular genre of Indonesian cinema, accounting for 60% of the 258 movies made in the country last year, according to the Indonesian Film Board.
But these aren’t like many of the scary movies shown in theaters across the United States, in which fright itself is the point. Indonesia’s horror boom is built upon the archipelago’s rich folklore, passed down from generation to generation, and an enduring belief in the supernatural.
All countries have their own sort of ghost story, says Dr. Imanjaya, a film studies lecturer at Bina Nusantara University in Jakarta, but “many Indonesian people believe that it’s true.” Indonesians’ fascination with their country’s unique blend of Islam and folklore has helped the local film industry thrive, while those in other developing nations struggle to compete with American blockbusters.
“We are very close to this folklore, this urban legend,” explains Dr. Imanjaya. People “like to be frightened with something familiar.”
Lindsey McGinnis/The Christian Science Monitor
Ekky Imanjaya, a film studies lecturer at Bina Nusantara University in Jakarta, Indonesia, stands outside the mall where “Haunting of Mount Gede” was playing in Tangerang, Indonesia, March 4, 2025.
Scared – and reassured – by the supernatural
References to the supernatural appear everywhere in Indonesia, the world’s largest Muslim nation. The city of Pontianak takes its name from a vengeful female spirit that the city’s founding sultan is said to have expelled in the late 1700s. During the height of the COVID-19 pandemic, a village in Java used patrollers dressed as ghosts to deter people from leaving their houses. And in a Jakarta museum dedicated to traditional Indonesian puppetry, a small wooden figure with a sheer, scarlet headscarf depicts the “Sweet Maiden of Ancol Bridge” – a woman who, according to legend, still haunts the bridge in northern Jakarta where she died.
Wayang Museum librarian Dwi Nur Ratnasari says this connection with the supernatural predates the arrival of organized religion in the first century.
“Before religion came to Indonesia, we believed in animism and dynamism,” she says. Back then, it would be common for Indonesians to pray to the spirits of a tree or stone. These beliefs blended with Hinduism and Buddhism, and when Islam began to spread through the archipelago in the 1200s, the culture evolved further.
Today, more than 87% of Indonesians identify as Muslim. Only 0.04% put themselves in the “folk/other” category. Yet a widespread reverence for local ghosts and other folklore persists.
“We still believe in ghosts,” says Ms. Ratnasari. “We acknowledge their existence amongst us; they are there as part of our universe. But we cannot worship them.”
Today, these spirits, known as danyang, are treated like neighbors that “we need to respect,” says Dr. Imanjaya. Offending them, many Indonesians believe, can invite tragedy, chaos – or a good movie plot.
Lindsey McGinnis/The Christian Science Monitor
A rainbow stretches over the Kapuas River in Pontianak, Indonesia – a multifaith city that shares its name with a vengeful female spirit from Indonesian folklore, Feb. 27, 2025.
Indonesian horror films improve
“Haunting of Mount Gede” has all the fixings of a modern Indonesian fright night: a host of angry danyang, an evil jinni (Islamic phantom), and a plot inspired by real-life events.
What audiences won’t find are common Western horror tropes, such as when Hollywood protagonists hear a strange noise and “get curious,” says Dr. Imanjaya, pantomiming a character sheepishly peering around a corner to investigate a disturbance.
“I don’t do that,” he laughs, waving his hand. “If I got scared, I’d pray with something from the Holy Quran.”
That’s how the protagonists in most Indonesian films react, too. They turn to Islam as a source of comfort and protection, and rarely waste time debating whether ghosts exist. When Itha returns from Mount Gede possessed by a mysterious spirit, her family immediately calls an ustad, or Islamic scholar, to try to heal her.
It’s these kinds of details that draw millions of Indonesians to theaters every year. Many international horror fans enjoy them as well. As streaming platforms carry Indonesian films to new audiences, foreign investment from Netflix, HBO, and other media giants has raised production values – something moviegoer Rifki Yusuf appreciates.
“Indonesian horror movies are gradually becoming a lot better,” he says, leaving the theater after watching “Haunting on Mount Gede.”
Mr. Yusuf, who came to the movies after his morning shift at a food manufacturing plant, says he didn’t find the film very scary. But he loved the cinematography and enjoyed the chance to reminisce about his own hikes up Mount Gede. He has been to the mountain five times, and for him, the creatures depicted in the film are more than just theater. “I know they are there,” he says.
Ismira Lutfia Tisnadibrata supported reporting for this story.
In an interview with Pharmacy Times®, Joshua K. Sabari, MD, assistant professor at the Department of Medicine at NYU Grossman School of Medicine, discussed zongertinib’s (Hernexeos; Boehringer Ingelheim) most common adverse events and its positive impact on patients’ daily lives. Sabari noted that pharmacists should monitor for diarrhea and mild liver enzyme elevations, especially during the first 12 weeks of treatment. Unlike intravenous therapies, zongertinib provides stable symptom relief and functional status, offering patients a convenient oral option with fewer chemotherapy-like toxicities and a significantly improved quality of life.
This is part 2 of a 3-part video series. You can watch part one here.
This transcript was edited for grammar and clarity using artificial intelligence.
Pharmacy Times:What key adverse events should pharmacists and clinicians be prepared to manage with zongertinib tablets, and what counseling points are crucial for patients starting this treatment?
Key Takeaways
Pharmacists should monitor diarrhea and liver enzymes closely during early zongertinib therapy.
Oral therapy allows patients to maintain stable symptom control without frequent clinic visits.
Zongertinib improves patient-reported outcomes compared to chemotherapy or IV antibody-drug conjugates.
Joshua K. Sabari, MD: Zongertinib is a HER2-specific tyrosine kinase inhibitor, and it spares EGFR, so we don’t see the cutaneous toxicities common with other HER2 and EGFR inhibitors. The most common adverse event is diarrhea. Grade 1 and grade 2 diarrhea occur in about 50% of patients, but grade 3, clinically significant diarrhea is low at about 1%. We also see mild elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in fewer than 10% of patients, so it’s important to monitor liver function tests every 2 weeks for the first 12 weeks of therapy. We don’t see cardiac dysfunction or significant interstitial lung disease. Overall, zongertinib is one of the better-tolerated targeted therapies available.
Pharmacy Times:For patients with HER2-mutant NSCLC, what does having an oral treatment option like zongertinib tablets mean for their daily lives, and what are the key advantages of this method over an intravenous therapy?
Sabari: When we meet a patient with stage 4 cancer, we explain that it’s treatable, but not curable. The goals of systemic therapy are to improve quality of life and hopefully extend survival. There are 3 types of systemic therapies: chemotherapy, immunotherapy, and true targeted therapy. An antibody-drug conjugate is essentially targeted chemotherapy—it has a warhead attached to an antibody, but the payload still causes chemotherapy-like toxicities. It also requires IV infusion once every 3 weeks, and patients often experience fatigue and nausea for several days after treatment.
With an oral therapy like zongertinib, how a patient feels on day 1 is how they’ll feel on day 3 or day 15. At ASCO 2025, we presented patient-reported outcomes showing dramatic improvements in symptoms like cough and shortness of breath, as well as overall functional status. These improvements remain stable over time. In contrast, patients treated with chemotherapy or antibody-drug conjugates often experience a steady decline in functional status due to side effects.
After a rapturous Venice bow for The Smashing Machine, Dwayne “The Rock” Johnson on Sunday talked about his next collaboration with director Ben Safdie for Lizard Music.
“I’m your Chicken Man,” Johnson recalled telling Safdie after he was pitched for 45 minutes on reteaming for Lizard Music after they wrapped production on The Smashing Machine. Their next joint project is based on the Daniel Pinkwater kids novel about a young boy who becomes involved with intelligent lizard musicians who tell him of a little-known invasion from outer space.
Johnson talked up Lizard Music as a “whimsical” movie about a boy who stumbles on a secret late-night broadcast of lizards playing music, only to pass through a hidden door to meet a Chicken Man, to be played by Johnson.
The Rock is in Toronto for a North American premiere of The Smashing Machine, where Johnson performs the role of real-life MMA legend Mark Kerr. “I wanted something like this for such a long time,” Johnson said during an informal conversation at TIFF at the Royal Alexandra Theater, about doing a movie creatively for himself, rather than acting in a Hollywood tentpole aimed at his legions of fans.
The Smashing Machine.
Cheryl Dunn/Venice Film Festival
Johnson recounted having to transform his own body into that of Mark Kerr. “He had this rare unicorn build of man who so dominant as a wrestler and with all of these fast twitch muscles, on top of being a heavyweight,” he recalled.
Long story short, Johnson had to gain weight for the role, and develop muscles other than his own frame to move more quickly in the ring. “He’s still a beast of a man, but still so soft-spoken,” he added about Kerr, who will attend the North American premiere in Toronto.
Johnson, as a former pro wrestler, also recalled as part of his transition to becoming a Hollywood movie star following in the footsteps of his late and Canadian father, Rocky Johnson, a WWE Hall of Famer, in getting into the ring.
“I think about my dad, about the complicated relationship we had, but how life can come full circle and years later I can come back and have this life,” Johnson said after touching down in Toronto. Born and raised in Nova Scotia as Wade Douglas Bowles, Rocky Johnson started wrestling in 1964 in and around Toronto.
His trajectory from the ring to Hollywood film sets includes roles in The Scorpion King, star turns in the Fast & Furious franchise, the Jumanji series and Disney tentpoles like the Moana films and the action-adventure Jungle Cruise.
“I remember a kid who was trying. I was just jumping off a cliff. That was the thing that really launched my career,” Johnson told the TIFF audience after watching a clip from The Scorpion Kings, which was shot in the Sahara desert and called for action sequences.
“From action to cut, I fell in love. I was bitten,” he said of catching the acting bug. At the same time, Johnson said it took a long time before he could bring his Hollywood acting chops to a more serious movie role. “I’d been wanting to do something like this, it just took all that time to do something like The Smashing Machine,” he added.
Johnson’s Hollywood career has also included work as a producer and co-owner of Seven Bucks Productions, launched in 2021 with partner Dany Garcia. “We loved movies, and if you love movies, you want to be part of creating movies in any way you can,” he said of launching the production banner whose name recalled his early attempt to join the Canadian Football League as part of the Calgary Stampeders as a path into the National Football League, only to be cut from the CFL team roster.
Back home in Florida, Johnson recalled looking into his pocket to see how much money he had at 22 years of age and having to move back in with his parents. He counted $7 in his pocked.
“We all get knocked down. Everybody goes through that,” Johnson recounted, as he also thanked former Stampeders coach Wally Buono, who is now with the B.C. Lions, for ultimately paving his way to big success in Hollywood after standing in his way from breaking into pro football.
Johnson was joined on stage in Toronto by co-stars Emily Blunt and writer/director Safdie. “When I first Dwayne, I saw this swirl behind his eyes. There’s this incredible magnetism that draws you in. but there’s also complex emotions just waiting to get out,” Safdie said of his need to collaborate with Johnson.
“We sat under this umbrella and talked and shared our souls. I was just taken by how different he was than what I had imagined,” Blunt recalled when first working with Johnson on Jungle Cruise in Hawaii as she discovered, as had Safdie, a vulnerability inside The Rock that was coming out.
Prime Video Australia has struck multi-year pay-1 window streaming deals with Sony Pictures Entertainment and Roadshow Films for their major global and local films.
The agreements, which began in August, means Prime Video is the exclusive streaming home to the likes of SPE’s 28 Years Later and Roadshow’s In the Grey.
From SPE are including Danny Boyle and Alex Garland’s 28 Years Later, Karate Kid: Legends, I Know What You Did Last Summer, Australian horror Bring Her Back, upcoming crime Caught Stealing and A Big Bold Beautiful Journey, the romantic drama starring Colin Farrell and Margot Robbie from filmmaker Kogonada.
The Roadshow includes Guy Ritchie’s In The Grey, Conclave, and a sequel to the young adult thriller Fall. Others includ The Monkey, Osgood Perkins directed horror film based on Stephen King’s short story; Made-Up Stories drama Addition – a drama from Made-Up Stories; and Den of Thieves 2 – the sequel to the 2018 crime film featuring Gerard Butler.
“By securing exclusive first streaming rights to films from Sony Pictures and Roadshow, we ensure Prime members get first access to stream these movies after their theatrical runs and digital rental windows,” said Tyler Bern, Head of Content Strategy and Content Acquisition for Canada, Australia and New Zealand. “This delivers more choice, more convenience, and incredible value for customers. Combined with premium content from Amazon MGM Studios, including our MGM theatrical slate, these deals ensure Australian movie lovers always have something exciting to stream.”
“We are thrilled to announce the extension of this content partnership with Prime Video in Australia,” said Adam Herr, Senior Vice President, Distribution, APAC, Sony Pictures Television. “Over the coming years, we have an exciting slate of theatrical films featuring some of the most iconic talent, directors and IP in Hollywood, and we can’t wait for audiences in Australia to enjoy them on Prime Video.”
“Roadshow is thrilled to extend our partnership with Prime Video,” said Will Meiklejohn, Director Acquisitions, Television & Home Entertainment, Roadshow Films Australia. “This agreement cements Prime Video as the home for the extraordinary films we’ve championed on the big screen, from powerful Australian stories to internationally loved blockbusters. It’s a natural evolution of our strong relationship with Prime Video and our shared commitment to delivering unforgettable cinematic experiences to audiences across the country.”
Prime Video has secured multi-year agreements with Sony Pictures Entertainment and Roadshow Films, making it the exclusive first-run streaming home in Australia for their Pay-1 theatrical slates.
The deals give Australian Prime members first access to blockbusters such as Sony’s “28 Years Later,” “I Know What You Did Last Summer” and “Karate Kid: Legends” — which reunites Jackie Chan and Ralph Macchio while introducing Ben Wang as a new Karate Kid — as well as Roadshow’s “In the Grey,” directed by Guy Ritchie and starring Henry Cavill and Jake Gyllenhaal.
“By securing exclusive first streaming rights to films from Sony Pictures and Roadshow, we ensure Prime members get first access to stream these movies after their theatrical runs and digital rental windows,” said Tyler Bern, head of content strategy and content acquisition for Canada, Australia and New Zealand. “This delivers more choice, more convenience, and incredible value for customers.”
The Sony slate also includes Darren Aronofsky’s crime caper “Caught Stealing” with Austin Butler, horror entry “Bring Her Back” from the creators of “Talk to Me,” and Kogonada’s romantic drama “A Big Bold Beautiful Journey” starring Colin Farrell and Margot Robbie. Roadshow will add award-winning films such as “Conclave,” and a sequel to the thriller “Fall.”
Other highlights slated for Prime Video include Osgood Perkins’ Stephen King adaptation “The Monkey” (Aug. 30), Made Up Stories’ drama “Addition,” and “Den of Thieves 2” starring Gerard Butler.
“We are thrilled to announce the extension of this content partnership with Prime Video in Australia,” said Adam Herr, senior VP, sistribution, APAC, Sony Pictures Television. “Over the coming years, we have an exciting slate of theatrical films featuring some of the most iconic talent, directors and IP in Hollywood.”
Will Meiklejohn, director acquisitions, television and home entertainment, Roadshow Films Australia, added: “This agreement cements Prime Video as the home for the extraordinary films we’ve championed on the big screen, from powerful Australian stories to internationally loved blockbusters.”
Prime Video already carries Amazon MGM Studios titles including “The Accountant 2,” “The Boys,” “Fallout” and “The Idea of You,” plus Australian originals “Deadloch” and “The Narrow Road to the Deep North,” alongside live sport such as ICC cricket.
