Half My Nightmares Start With This Giant Cyborg Teddy Bear Learning How to Hug – Gizmodo Australia

In a time of social distancing, a giant teddy bear giving enormous hugs sounds like a great way for people to safely cope with isolation. But Arizona State Universitys robo-bear, which can learn to hug by observing humans, looks like its ready to give you the last embrace youll ever feel.

As more and more robots are integrated into places of work like factories and distribution centres, they need to be able to safely co-exist and work alongside their human counterparts. To date, the solution has been to either to segregate robots and hide them behind protective barriers so humans cant get near them, or to pack them full of sensors so they can either autonomously avoid people or stop moving until its safe to do so again. Humans actually working with robots, and not just beside them, is still a concept mostly relegated to science fiction but researchers are working on it.

The biggest hurdle to overcome is that humans can be unpredictable, and attempting to pre-program a robot to account for every possible movement and interaction with one is an act of futility. How a human picks up a part and hands it to a robot for the next step in an assembly line could be slightly different every single time, which is why, more often than not, humans are instead trained to deal with robotic co-workers who can be programmed to be far more predictable. The problem with that approach is that it limits a robots abilities and adaptability, and for smaller companies who may have different needs for a robot day by day, it makes investing in the hardware less appealing. The ideal solution is a robot that can learn tasks, and how to deal with people, all on its own.

Thats what being demonstrated in this video shared by Arizona State Universitys Interactive Robotics Lab on YouTube. Its a continuation of research first published three years ago in a paper titled, Bayesian Interaction Primitives: A SLAM Approach to Human-Robot Interaction. Thats a mouthful, but the research involves teaching robots how to use their various sensors, including live feeds from video cameras, to not only figure out their environment and their location in it (SLAM is short for simultaneous localisation and mapping) but also to track the movements of a human and accurately predict their intended actions be it simply handing an object over for a robot to reach out and grab, or in this case, embracing a human in a hug.

By simply watching a human go through the motions a handful of times, the robot can effectively learn, all by itself, how to perform a hug. And its not limited to just the person who performed the initial demonstration. The robot learns how to mimic and perform these actions with anyone, no matter their shape or size, or even the motions they use to initiate the hug. By learning on its own, and coming up with generalizations that are refined through real-time observation, the robot can quickly assess that an incoming human is simply looking for affection hopefully.

By dressing the robot up as a giant plush teddy bear, the researchers are clearly trying to invoke an emotional response in test subjects so that the resulting hug is performed more authentically, like they were genuinely embracing another person. The only problem is that thanks to video games like Five Nights at Freddys, and the terrifying animatronic performers at restaurants like Chuck E. Cheese, its hard to imagine anyone approaching and embracing this dressed-up robot with anything but trepidation and terror. Death by robot teddy bear is now one more thing to genuinely worry about.

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Half My Nightmares Start With This Giant Cyborg Teddy Bear Learning How to Hug - Gizmodo Australia

The Worst Parts of Justice League Theatrical Cut, From Supermans CGI Mouth to That Underwater Battle – TheWrap

Justice League, while certainly never approaching the creative nadir that was the DC movie Suicide Squad, is really just not a good movie. Its silly-but-not-in-a-good-way, its nonsensical, its sort of inexplicably chaotic. Its exciting, then, that well eventually be able to compare Joss Whedons Justice League to the Snyder Cut next year and maybe get a better understanding of what went on here. But while we wait for that day, lets reflect on the pure madness of the theatrical version.

The Atlantis fight

James Wan, who is one of the best filmmakers working today, absolutely knocked all that underwater stuff out of the park in his standalone Aquaman. But the Atlantis fight in Justice League, on the other hand, was an absolute trash fire that looked just incredibly awful. Whatever Warner Bros. spent on this sequence, it was too much. Woof.

Steppenwolf repeatedly talking to mother

Justice League does a pretty poor job of explaining Steppenwolfs powerful artifacts, the Mother Boxes, which fans of the comics know are actually supercomputers with consciousness. Its even weirder when Steppenwolf occasionally talks out loud to Mother, telling her (?) hell be feeding her soon and dropping some other weird lines. The movie never explains that the boxes are actually alive and bond with their owners so strongly that they will self-destruct if the person to whom theyre linked are killed.

Anyway, presumably hes talking to the box(es). Maybe Justice League is actually about a guy with a computer pet whos just trying to be a good friend and get it some snacks.

Also Read: Every DC Comics Movie Ranked From Worst to Best, Including 'Justice League'

For Darkseid!

Fans who know something about Steppenwolf know that hes actually a lieutenant of Darkseid, a supervillain arch-nemesis of the Justice League whos bent on conquering the universe. For everyone else, Steppenwolf is a pretty obscure character, so his single off-handed mention of the fact hes doing evil stuff for Darkseid is easy to miss and fairly confusing particularly if you dont know who Darkseid is and thought he said Dark Side. One assumes Justice League was, at one point, setting up for Darkseids eventual arrival. The movie as it exists is not, aside from that single line.

Since Darkseid figured majorly into Zack Snyders plans for Justice League and its sequel that didnt end up happening, we should at least finally get some context for this line in the Snyder Cut.

#Supermouth

Paramount wouldnt let Henry Cavill shave his Mission: Impossible Fallout mustache during Justice League reshoots, so Warner Bros. decided theyd just try to digitally remove it in post-production. And it is absolutely horrifying. Its worse than CGI Peter Cushing in Rogue One a cartoon-looking mouth on an otherwise human face will always look more upsetting than that entire cartoon-looking face. Our brains just cant even fathom this thing.

If, for whatever reason, youd like to bask in the horror that is Supermans CGI mouth, check out our gallery of the most terrifying shots of that cartoon monstrosity.

Also Read: The 10 Most Terrifying Shots of Superman's CGI Mouth in 'Justice League' (Photos)

That opening Superman scene

This weird little home video segment of a kid talking to Supes is a double whammy of existential pain. First, you have the whole CGI mouth thing, which is extremely obvious throughout. Then you have Superman refusing to answer the kids question about what his favorite thing about living on Earth is. Theres no thematic payoff to the scene later in the movie, and so it plays like the movie is just trying to dunk on itself.

Clark and Lois hanging out in a CGI cornfield

If youre going to do an extended green screen scene, maybe its best not to throw an extremely colorful, eye-catching background behind your characters. Nobody told Justice League this, though, and so theres a touching scene between Lois Lane (Amy Adams) and Superman standing in a cornfield in Kansas that is extremely, obviously not real. The culprit is probably that glaring gorgeous sunset that makes the outline of the characters a little too obvious. The emotional reunion of Lois and Clark gets seriously undercut by the fact that nobody can stop thinking about how theyre standing on a soundstage. Throw in Supermans gross CGI smile in for good measure and the whole thing turns into a very dry comedy sketch.

Also Read: 'Justice League': What The Hell Is the Deal With Steppenwolf's Mother Boxes?

Nobody really cared about Superman returning

Justice League makes a big deal about Superman being dead. Its such a blow to the world that crime and terrorism are on the rise thanks to the simple lack of hope he embodied. So resurrecting Superman mid-movie seems like it ought to be a pretty big deal, especially as it is witnessed by at least a few civilians and results and in a big public fight with at least one somewhat-publicly known hero. But almost no acknowledgment is made of Supermans return, and while his effect on the world is part of the movies setup, its not at all part of the rest of the plot. Theres no celebration, no montage of racists not being racist anymore to call back to the opening credits. Hes just back, and the movie itself seems to care about that about as much as those ancient humans cared about the security of their Mother Box. Plus Clark Kent was dead too. Is Superman just going to skip the alter-ego thing from now on or what?

Using the were gonna do a thing that will bring the bad guy down on us trope but no one having any clue that theyre doing it

When the Justice League decides to use a Mother Box to resurrect Superman, it seems pretty obvious that doing so will attract the attention of the villain who has spent the whole movie trying to round up all the Mother Boxes. Well, its obvious to us, anyway, because weve all seen a hundred movies, TV shows and video games with that specific trope you know, the OK, so we have to flip this switch in order to do something important but its definitely going to attract the bad guys to us and cause a big fight trope. Its not so obvious to the characters in the movie, though, because they never mention the possibility that Steppenwolf will show up and seem weirdly surprised when he pops in to steal the box right under everyones noses. I guess they forgot to make this scene make sense when they rejiggered the plot during reshoots.

Also Read: 'Justice League' Post-Credits Scene Explained

Cyborg is extremely not stealthy

Cyborg (Ray Fisher) wears a hoodie when he goes out, but it does almost nothing to contain the fact that he has extremely obvious glowing lights in his face and chest. He also makes a lot of very ominous whirring sounds just by being alive. So it was pretty tough to buy that he was stealthily spying on Diana Prince and Bruce Wayne to suss out their deal before joining the nascent Justice League, as he was only about 25 feet away and making a lot of loud weird robot sounds. At least Diana said she was fully aware of him watching just one scene later. But still, youd think his computer brain would have been slightly smarter.

Cyborgs nonsensical origin recap

Introducing Cyborg in a team-up movie was never a great idea, but it takes quite a while for Justice League to explain what his deal even is. Injured in an explosion, Vic Stones cool superpowers are the result of interference by one of Steppenwolfs weirdo Mother Boxes. The apparently sentient supercomputer of incredible power actually reshaped state-of-the-art cyborg enhancements his father Silas gave him in order to save his life after an accident. The result is that Cyborg doesnt even know what his abilities are and, also, that nobody explains who he is or why hes a spiffy alien robot man until about halfway through the movie. The rest of the time, the audience has to sit there, confused.

Cyborg cant control his defense system

The good guys resurrect Superman, who immediately gets mad and makes threatening faces and stuff. And in a moment that is completely out of step with the rest of the movie, Cyborgs cyborg parts start doing their own thing without his input. There had been no hint before then that that could happen, and it doesnt happen again even though Cyborg doesnt appear to take any measures to prevent that situation from arising a second time. Nobody even has the, Yo, man, is this gonna be a problem? conversation with him.

Also Read: 'Justice League' Fans React to Henry Cavill's Mustache Removal: 'This Is F-king Real?!'

The ancient people who buried a Mother Box in a 3-foot deep hole next to a river

The first time Steppenwolf tried to take over Earth way back when, he was defeated by an alliance of the Old Gods, the Amazons, the Atlantians and the humans, who took his Mother Boxes entrusted to each of the civilizations to keep them safe. The Atlantians put theirs in the ocean; the Amazonians built a giant stone vault; and the humans dug a 3-foot hole next to a river and tossed their box in it. This is not the best way to hide, like, anything. Its probably not a coincidence that this Mother Box is the only one that didnt stay where it was for the next 5,000 years. A dog probably dug it up the next day.

The Russian family the movie keeps cutting to

Superhero movies will often throw a few random civilians in harms way in order to show the stakes of the situation. Justice League spends several scenes hanging around with a random Russian family who lives unfortunately close to Steppenwolfs apocalyptic base, hoping to set up a last-second rescue much, much later in the movie. In the meantime, though, this family is stuck in their house hiding from monsters for, like, a week. They never get any characterization or do anything and none of the several scenes about them do anything to push the story forward. This is extremely not how to get the audience to care about regular people in the middle of supervillain danger.

Also Read: Will the 'Justice League' Snyder Cut Actually Deliver What Fans Asked For?

Superman showing up and being easily capable of winning the fight at any moment

The Justice Leagues final fight with Steppenwolf doesnt exactly go poorly but, as weve seen demonstrated multiple times in the movie before, hes seemingly a match for any of the super-strong members of the team, and maybe even for all of them put together. Enter Superman, who dodges Steppenwolfs attacks, pummels him about the face, and is generally capable of putting the supervillain down without a lot of help. But thats not especially dramatic so Superman bails mid-fight to go save a building full of civilians. Having a guy on the team who can handle basically any problem on his own kind of undercuts the need for a team, and it sure feels like Justice League is looking for a way to get Superman out of there as soon as he shows up. Poor planning for your climax, that.

Diana doing The Flash thing and then forgetting she can do that for the rest of the movie

Wonder Womans (Gal Gadot) introductory scene in Justice League is actually pretty cool. A terrorist group takes over a bank intent on exploding a bomb that will wipe out several city blocks, apparently because they think that will help push society back to the Dark Ages, which is a good thing for some reason. Whatever Diana beating people up is what matters, and that goes pretty well. Until, that is, terrorist leader Roose Bolton levels a machine gun on the hostages. Rather than take him out, Wonder Woman moves super-fast to block all of the dozens of bullets he fires with her gauntlet (and casually move one guy out of the way). We know Wonder Woman is extremely super, but apparently racing bullets is now in her repertoire. Kind of makes The Flash (Ezra Miller) obsolete. Then again, she doesnt use this ability for the rest of the film, even when it would have been super useful in the various fights with Steppenwolf.

What does that smell like? Fear

While it was a little frustrating that Superman could have obviously ended the battle with Steppenwolf whenever he felt like, it was just plain goofy what finally brought him down in the end. An earlier, easily missed line in Justice League pointed out that his henchmen, parademons, feed on or otherwise are attracted to fear. So when Superman et al. started really giving it to Steppenwolf in a way that suggested he might not win, Batman (Ben Affleck) and Aquaman (Jason Momoa) took a second to point out that he was afraid. The exchange itself was weird Aquaman asking, What does that smell like? and Batman responding, Fear but then Steppenwolf was overwhelmed as his own troopers suddenly decided to turn on him. This was a guy that was batting away Amazons like they were actually insects earlier in the movie, mind you, so his ultimate defeat at the hands of his own not-especially smart bugmen felt pretty forced. LOL.

(Spoilers ahead for "Justice League")Given that the Joss Whedon-helmed reshoots on "Justice League" went on significantly longer than planned, it's not really a surprise that some scenes from the marketing didn't make the final cut. But it's still fun to take a look at what was meant to be and compare it to what we actually got. So let's do that right now.(Note: This post was originally published on Nov. 18, 2017)

This hero shot of Wonder Woman (Gal Gadot), Aquaman (Jason Momoa) and Cyborg (Ray Fisher) didn't make the movie -- and neither did whatever location they're standing in.

This location appears to be a different version of the cross-shaped platform at the center of the abandoned nuclear reactor Steppenwolf works from in the movie, but it never ends up looking so thoroughly thoroughly alien in the finished film. This old version of that space may have been somewhere else -- like inside Steppenwolf's spaceship that he keeps teleporting down to Earth from but which we never actually see in the movie.

There were two trailer shots that showed Victor Stone in his pre-Cyborg state, but none were in the movie.

Here's Victor Stone playing football, another pre-Cyborg bit for him that didn't make it in.

There is a big cornfield scene between Clark (Henry Cavill) and Lois (Amy Adams) in the finished film but either it's different from this one one -- in which Clark says that he'll take her wearing his engagement ring from "Batman v Superman" as a yes to his proposal -- from the trailer or this was a part of that scene that didn't make it in. The cornfield scene in the finished product, notably, is one of those where Henry Cavill has his "Mission: Impossible" mustache being covered up by CGI, and that is very obviously not happening in this shot here.

Though the "Justice League" opening credits did feature a montage of people being terrible without the moral compass of Superman to guide them, this bit with the "WORLD WITHOUT HOPE" newspaper headline was not among those shots.

There's a scene in which Alfred (Jeremy Irons) is talking to someone offscreen (it's implied that it's Superman) in the batcave. Based on the dialogue we'd guess that Superman visited Alfred to find out where the other Justice League pals had gone to fight the final battle -- Superman, as you'll recall, simply shows up midway through that fight.

There was a bit in one of the trailers where Cyborg saves a man from being nailed by an exploding tank, but there were no tanks at all in the finished film so it's tough to guess where this fits in.

Aquaman did spear a lot of bug people in the finished movie, but this bit where he spears two at the same time didn't make the cut

This trailer shot shows Cyborg sporting a helmet.

The trailer implies this shot is of Cyborg flying above the clouds, and while we do see him fly around a few times we never got this particular bit.

The Flash breaking a window while using his super speed was a cool visual that was nowhere to be found in the finished movie

Here we see the Flash (Ezra Miller) fighting an evil soldier. Curiously, that entire type of baddie was cut from the movie -- all of Steppenwolf's forces had wings but this guy looks more like a regular human, a la the soldiers in Bruce Wayne's nightmare in "Batman v Superman."

Not sure what this shot is, honestly.

This part, in which Wonder Woman knocks a couple bug guys off the Batmobile, actually is in the movie -- but the color pallette is dramatically different in the finished film, sporting a bright red hue instead.

Weve got a pretty solid amount of cut content to sift through here

(Spoilers ahead for "Justice League")Given that the Joss Whedon-helmed reshoots on "Justice League" went on significantly longer than planned, it's not really a surprise that some scenes from the marketing didn't make the final cut. But it's still fun to take a look at what was meant to be and compare it to what we actually got. So let's do that right now.(Note: This post was originally published on Nov. 18, 2017)

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The Worst Parts of Justice League Theatrical Cut, From Supermans CGI Mouth to That Underwater Battle - TheWrap

What Is The Justice League Snyder Cut Explained | Screen Rant – Screen Rant

After years of rumors and speculation, Zack Snyders Justice League cut will finally be released on HBO Max in 2021. The troubled production of the original 2017 version combined with disappointment from fans created a movement for the release of Zack Snyders original vision. Despite initial denials from the studio, the Snyder Cut was confirmed to exist in 2019 and was recently announced as an HBO Max exclusive. But what exactly is this version of Justice League? And what does it mean for the industry?

Director Zack Snydergave birth to the DC Cinematic Universewith Man of Steelafter Christopher Nolans Dark Knight trilogy finished in 2012. The choice made sense to Warner Bros. as Snyder had experience adapting comic books and graphic novels to the big screen after directing Watchmen and 300. The studio's hope was the directors unique style would distinguish the DCEU from Marvels cinematic universe, using DCs classic superheroes to surpass Marvels success at the box office.

Related: Everyone Was Wrong About Justice Leagues Snyder Cut

In 2013, Snyders Man of Steel was released, followed by 2016s Batman v Superman: Dawn of Justice. Despite earning over $1.5 billion combined globally, both movies proved divisive with critics and audiences anddidn't match the same box officehighs by the Marvel movies at the time. The future of DCs expanded universe seemed to be on shaky grounds. While the script for Justice Leaguewas completed before the release ofBatman v Superman: Dawn of Justice, the negative reception resulted in Snyder and Terrio rewriting their script before starting production onJustice League.Shooting wrapped in December 2016, and Cyborg actor Ray Fisher said there was enough shot to make two movies. Snyder's early assembly cut wasfive hours, and he says his director's cut was overthree-and-a-half hours long. He screened a two-hour cut for the studio, but they weren't satisfied and assembled a writers room to implement changes to Snyder. Unfortunately, before he could complete another version, Snyder had to step away from his directing duties due to a family tragedy. To finish production, Warner Bros. hired director Joss Whedon.

Even before Snyders exit, studio executives were already pushing for creative changes. Producers Jon Berg and Geoff John were brought on the project to make Justice League more hopeful and optimistic. It was clear Warner Bros. wanted to move away from Snyders darker style after the reception of Batman v Superman. Snyders departure and Whedons involvement represented an opportunity for the studio to change the movie even further. However, they had no intention of pushing back the release date.

The new director adding about 80 new pages to the script, earning him a screenplay credit. Asignificant chunk of Snyders footage was tossed in favor of a two-month reshoot. Scenes with more humor and a brighter tone replaced the more violent ones from Snyders version. Comic book lore and characters backstories were cut. A conflicting schedule with Mission: Impossible Fallout meant actor Henry Cavills mustache had to be removed digitally from every Superman scene. The production cost also went up, adding at least $25 million to the films budget.

The result was a movie stitched together from multiple tones, often referred to as a "Frankenstein movie" failing to please audiences. It earned $658 million worldwide, a disappointing sumby any standard.

Dissatisfied with Whedons Justice League and upset with WB's treatment of Snyder,fans created an online petition calling for Warner Bros. to release Snyders original cut. To them, the movie in theaters didnt realize Snyders vision as promised by the studio. The petition gathered almost 180,000 signatures and started a movement that would later adopt the hashtag #ReleaseTheSnyderCut. In 2018, a website was created to draw attention to the cut by a fan named Fiona Zheng and would become a gathering spot for fans. ForSnyderCut.com organized a photoshoot of cosplayers holding a banner outside the Warner Bros. studios to promote the campaign.

Fan efforts would continue for two-and-a-half years despite a release being considered far-fetched by industry insiders. The campaign did mass letter-writing drives, paid for billboards near conventions and Times Square, and raised over $150,000 for suicide prevention, all hoping to convince Warner Bros to release the directors cut. Unfortunately, some also harassed those critical of the movement, such as journalists and former DC Entertainment president Diane Nelson.

Related:Here's Why We Still Care About Snyder's Cut

Overall enthusiasm for the Snyder Cut remained strong long after the original Justice League, especially because many of the cast and crew voiced their wish for the release. Snyder was thankful for all the fan support. He also helped fuel excitement for the cut when, in early 2018, he began releasing still images and storyboards from his version of the movie on social media. The director would continue to share these tidbitsand outright confirmed he had a cut of the movie in 2019. Yet the decision to release it still had to come from Warner Bros, so the campaign persisted. On the two-year anniversary ofJustice League's release, the #ReleasetheSnyderCut became the top trending topic on Twitter, withnearly 1 million tweets. This is reportedly the moment when fans convinced AT&T and Warner Media to change their mind.

Over the years, details about the Snyder Cut began to emerge. The basic plot with the League uniting to fight against Steppenwolf and the Mother boxes isbasicallythe same; however, many things were cut, including the backstories for new characters, some characters were removed entirely, and multiple subplots were removed or replaced. Besides story changes, the Snyder Cut will also have a different tone than the theatrical release. While Snyder always said Justice Leaguewould be lighter thanBatman v Superman,Whedons numerous additional jokes and quips wont be part of this version, and the overall colors will be less oversaturated, particularly in the final battle.

Theres a lot more backstory for Aquaman, Flash, and Cyborg in the Snyder Cut. Since Justice League would be their first official cinematic appearance, Snyder wanted to introduce them properly something Whedon struggled to achieve. These scenes contain other side characters such as Iris West, Cyborgs mother, and Martian Manhunter. Cyborgs role will be muchbigger hes described as the heart of the movie. More scenes with his father and his life pre-transformation are expected. Hopefully, this will translate into better-developed characters the audience can enjoy.

Related:Could Snyder's Full Original DCEU Slate Still Be Completed?

Another change will be Supermans storyline as Whedon modified his resurrection arc significantly. In Snyders version, the entire League appears to be involved in his digging up his grave, and Cyborg is the one who comes with the idea of using the Mother Box to bring back Clark. After being brought to life, Clark also is shown visiting a Kryptonian ship to get his suit back.

Finally, Snyders original plan was to set up Darkseid as the future main villain of the series, with Steppenwolf simply being his agent in Justice League. Much like Thanos first introduction, or Sauron in the Lord of the Rings,Darkseid would be present as a shadowy figure or, perhaps, showing up in the History Lesson flashback, with a few teases throughout the rest of the movie, and a major cliffhanger ending teasing his impending invasion. Its unclear how much material of him will be in the cut, considering his role as the main villain would only happen in later movies.

Theres no doubt that the Snyder Cut is a special case. Studios and directors have clashed creatively before, and ultimate cuts and extended versions of movies have been released over the years, but nothing quite like this. Even Blade Runner, which is famous for its multiple versions (the latest made in 2007, 25 years after its original release), and director Richard Donner's Superman II didnt go as far as spend well over$30million to add to and complete the Snyder Cut. Bringing the Snyder cut to the screen means going beyond the addition of unused footage. An investment this big requires a studio believing they will turn a profit. This is where #ReleaseTheSnyderCut comes in.

Another aspect that is unique to the Snyder Cut is the persistence of the fan campaign behind the hashtag. Even after three years, the excitement never died down. Instead, efforts became increasingly professional, and no doubt this was seen by HBO and the studio as a sign it was worth the money to give fans what they wanted. The push for a release by fans combined with the need for original and exclusive content for HBO Maxs launch represents a perfect storm that is unlikely to happen again. Yet, this might set a precedent for fan-backed directors cuts finding new homes with streaming services.

But not everyone thinks the release of the Snyder Cut is a good thing. Some people are worried about studios fueling fan entitlement by releasing it. There are those who believe the toxicitypresent in elements of#ReleaseTheSnyderCut should've not been rewarded. Also, while the Snyder Cut was a fan movement, not all DC fans like the director. There is a part of the fandom who strongly dislikes his gritty version of Superman and other DC superheroes. To them, this is a sign DC and Warner Media arefollowing a creative path they have hated for a long time.

More: What About Justice League Part 2?

Key Release Dates

Justice League: First Official Image Darkseid From Snyder Cut

Priscila Santa Rosa is an avid TV and movie fan. She covers entertainment news.

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What Is The Justice League Snyder Cut Explained | Screen Rant - Screen Rant

New biomimetic eye research could indicate the future of prosthetic, super-human eyes – Pocket-lint

When it comes to the realms of science fiction and speculation, we've got a bit of a fascination with eyes, you might have noticed. Whether it's the refrigerated swap-shop in Blade Runner, an endless list of red-overlaid robot's eye views from the likes of The Terminator or Robocop, or using their expressive nature as a window the soul in I, Robot or AI, they feature constantly in films about robots and cyborgs.

Well, don't get too comfortable with the idea that these prosthetics are decades or centuries away - scientists are hard at work on manufactured eyes that could even supercede the ability of the homegrown human version.

In fact, a publication in prestigious journal Nature this week has brought this even closer to reality, detailing the work of aProfessor Zhiyong Fan, from the Hong Kong University of Science and Technology, who's been working for some time on bionic eyes.

His and his team's new paper, elegantly titled "A biomimetic eye with a hemispherical perovskite nanowire array retina", details a 3D entirely artificial eyeball that they've built, which effectively mimics the actions of the human eye.

As the paper's abstract affirms, it's worth remembering that the human eye is insanely sophisticated - compare its field of view, resolution and colour-sensing to any of the world's most expensive cameras and that'll be underlined.

The team used a dense array of nanowires to apparently replace the photoreceptors used by the human eye's retina, which has been a stumbling block for other projects. It's able to sense and detect objects with a good deal of precision, as a result - in fact, it has 30 more photoreceptors than the human eye, making for a potentially superior degree of perception, eventually.

This potentially opens the way for a heck of a lot of applications, most of them likely not involving a creepy human-looking eye surveying processes, but also for the continued development of what are effectively cybernetic implants. It's a brave new world out there, folks.

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New biomimetic eye research could indicate the future of prosthetic, super-human eyes - Pocket-lint

Demos for System Shock, Destroy All Humans, and five other upcoming games popped up on GOG – Destructoid

SHODAN sends her regards

Demos for seven upcoming PC games are playable today on GOG just in time for the store's 2020 Summer Sale, and they're absolutely worth a look. You might not be into all of them and you probably aren't even familiar with a couple but I'm willing to bet at least one of the demos will speak to you.

The list includes Desperados III, System Shock, Destroy All Humans, Cris Tales, Vagrus - The Riven Realms: Prologue, Spiritfarer, and Carrion. I'm making a beeline for the two remakes, and then I'll try to loop back for Cris Tales it's aiming to blend classic (Chrono Trigger) and modern (Persona 5) JRPG sensibilities.

Some of the demos are on the shorter side, but then there's Desperadoes III. It's over 90 minutes!

So far, I've only played the System Shock alpha demo, and I like what Nightdive is doing.

As you can see in the screenshots I captured below, this revival is super faithful to the original but it doesn't feel dated. It's riding that line. In the demo, I woke up, inputted the classic keycode, smashed several mutants with a lead pipe, loaded my inventory with items I wanted to save for later but never got around to using (big mood!), and was ultimately gunned down by a cyborg. A fitting end.

While the combat is a little fiddly right now, Citadel Station's ambiance is there in spades. I was sufficiently spooked. I'm not sure if anyone will be truly "blown away" I kind of doubt it, actually but as far as remakes of beloved 25-plus-year-old games go, I respect Nightdive's commitment to detail.

Beyond the cool multi-demo promo, the wider GOG 2020 Summer Sale runs until Monday, June 15. Metro Exodus: Gold Edition ($29.24) and Prey: Digital Deluxe Edition ($11.99) are currently topping the best-seller list, but there are 3,000-some deals on the site. Check your wishlist if you have one.

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Demos for System Shock, Destroy All Humans, and five other upcoming games popped up on GOG - Destructoid

Darkseid’s Greatest Weapon is Nothing To Wonder Woman – Screen Rant

In this Justice League's comic origin story, Darkseid invades Earth with his armies, and Wonder Woman is faster than a speeding Omega Beam.

Darkseid is infamous for being one of the few villains that can take the entire Justice League, but one time Wonder Woman got the better of him alone. In the middle of a full on earth invasion - parademons swarming, League members falling left and right - Wonder Woman knocks aside a blast from Darkseids Omega Beams and dispatches the New God in stunning fashion.

These heroics take place in issue #6 of New 52 Justice League, by Geoff Johns and Jim Lee. Over the first six issues, the League comes together for the first time in a world where people barely know what superheroes are. Batman and Green Lantern kick the action off when theyre drawn to the presence of a Motherbox in Gotham City. As the ensemble grows and pursues their mystery, Victor Stone transforms into Cyborg. Fans have heard his origin story retold again and again by now, but this appearance marks his first as a member of the Justice League.

Related: Batman Isn't Afraid of Any Superhero... Except Wonder Woman

Superman takes an attack full in the chest, so hes carried away to be experimented on by Apokoliptian scientists. That means the gang is short handed when they face Darkseid in an open field battle. At one point, Aquaman valiantly tells a shark to leap out of the water and devour a parademon, but the battle still isnt going their way. Naturally, they were playing to their individual strengths instead of working as a team. As soon as they regroup, Wonder Woman has the support to try and blind Darkseid. He shoots an Omega Beam right at her, but she blocks it with her gauntlets. This throws him off just enough to give her the advantage. A leaping sword attack stabs him right in the eye.

Besides an apparent power upgrade, the New 52 held mixed results for Wonder Woman. Her origin and family were reconnected to the Greek Gods, but romance still plagued her storylines, and that costume was clearly over the top. Later in the Justice League run, shes the first to encounter Grail, Darkseids daughter, in a rivalry that lasts to this day. The mythological family tree has stuck too. Dianas life is still constantly interrupted when a helpless/dangerous relative of some obscure/symbolic God falls at her doorstep.

While reading an origin story about these heroes coming together - especially one in which Cyborgs transformation coincides with a Darkseid invasion - a fan cant help but think of the upcoming Snyder Cut. But theres an x-factor that comes out in this story when the team is assembled. The chemistry of that movie would have to come a long way to even match this New 52 meet-cute. Green Lantern in the mix throws a great wrench in the Batman/Superman/Wonder Woman triumvirate. Flashs purity of heart adds an innocence that lightens the overwhelming tone. Aquaman still desperately searches for ways his powers can help.

No matter what moves Wonder Woman has, Darkseid is sure to be back on the page and screen. This is the kind of League that can take him.

Next - How Darkseid Originally Killed Batman in the Comics

Hulk Almost Killed Marvel's THING With A Single Punch

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Darkseid's Greatest Weapon is Nothing To Wonder Woman - Screen Rant

Henry Cavill will be back as Supermansomewhere – The A.V. Club

Photo: Visual China Group (Getty Images)

Even as internet sharks circle the (surprisingly expensive) news that HBO Max will be playing host to a re-cut version of Zack Snyders Justice League next year, the members of the League itself remain doggedly difficult to track down. Batmans just gone, of course, with Ben Affleck having flown the belfry shortly after the films release back in 2017. But even the more technically-extant members of the superhero squad are being a little aloof these days, what with The Flash having been in development for roughly a decade, Cyborg going AWOL, and Wonder Woman aggressively doing her own thing. As Warner Bros. has attempted to salvage the only-moderately-profitable situation by scaling down plans, focusing on individual characters, and pulling back from the shared universe stuff, chaos has inevitably reigned. Harley Quinn suddenly has more movies than Batman; Aquaman is a major box office draw; the Batmobile broke a wheel, and now theres, like, six Jokers roving around out there.

Which raises the question: Whither Superman? We havent seen Henry Cavills take on DC Comics iconic good guy for three years now, ever since he and his suspiciously absent mustache saved the day from Steppenwolf. (Steppenwolf: Still the bad guy from Justice League!) Shazam! even ends with Superman showing up at Billy Batsons school as a plot point, but Cavill himself never appears. (They used Zachary Levis stuntman for it, instead.) Heck, he didnt even show up for The CWs big Crisis crossover, and they even got Smallvilles Tom Welling for that one.

But the Man Of Steels (fortress of) solitude might be about to crumble. Deadline reports that Cavill is apparently in talks to reprise the role of Supermanalthough, hilariously, no one appears to know where. The article makes it fairly clear that Man Of Steel 2 is definitely not on the table, but doesnt specify where else he might reasonably cameo. Shazam 2 and Black Adam, set for November 2022 and December 2021, respectively, might be a reasonable guess, but wed like to pretend that Supes will be showing up for The Trench, that movie about the fish monsters from Aquaman that Warner Bros. once floated the idea of making. Wherever he pops up, itll presumably be somewhere where having, yknow, Superman on hand wont immediately solve the problem. But theyll also need it to be at least semi-substantial; you dont want to force Cavill to shave again for nothing, right?

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Henry Cavill will be back as Supermansomewhere - The A.V. Club

Cell and gene therapies – Lexology

In recent years, we have seen a trend towards the launch of new gene and cell therapies with record-breaking price tags. Such headline-grabbing launches are becoming more and more frequent, as the pipeline for advanced therapies at all stages of development continues to grow at a rapid pace[1]. We are also seeing industry and payers adopting new innovative pricing models for those products, such as outcome-based reimbursement and annuity payment models. In this article, we discuss these emerging alternative pricing models and consider the impact they may have on related licensing arrangements.

Current trends

In May 2019 AveXis, a subsidiary of pharmaceutical giant Novartis, announced that it had received approval from the US Food and Drug Administration to market its gene therapy Zolgensma for the treatment of paediatric patients with spinal muscular atrophy (SMA). Although this is the first promise of a cure for this debilitating and lethal condition, the media coverage focussed instead on Zolgensmas price tag, which at $2.1 million per patient makes it (currently) the worlds most expensive single-dose medicine.

Zolgensma is illustrative of a general trend in gene and cell therapies that have reached the market in recent years and established a new standard of pricing for single-treatment medicines. While manufacturers point to the relative cost-effectiveness of such treatments (which may offer a one-off cure for severe conditions that otherwise would require several years worth of conventional treatments and care) public and private payers are concerned about this new escalating pricing paradigm.

Health care systems may be able to absorb such high prices for rare diseases with small patient populations. However, the current reimbursement systems will be under severe pressure if (as is hoped) pipelines for advanced cell and gene therapies result in treatments for common conditions such as diabetes or heart disease. The Institute for Clinical and Economic Review in the US has estimated that if gene therapies are developed to treat only one in ten American patients with a genetic condition approximately 1% of the total population the cumulative budget impact could rise to $3 trillion[2]. For comparison, the projected total healthcare spend in the US for 2019 is $3.8 trillion[3].

Alternative Pricing Models

The pharmaceutical industry has sought to counter criticism over the high price tags for gene and cell therapies by coupling these revolutionary therapies with new and unconventional pricing and reimbursement mechanisms.

One alternative structure that has been adopted is an annuity based model which spreads the payment for an expensive treatment over several years in a pre-agreed payment plan, thus minimising the up-front cost to payers.

Another approach adopted by the industry, and perhaps an even clearer way to demonstrate value to payers, has been to tie reimbursement to patient outcomes. The industry has negotiated several of these outcomes-based reimbursement models with public and private payers for cell and gene therapies. Reimbursement payments to the drug maker under this model are conditional upon the patient reaching specific clinical outcomes by set deadlines. Depending on the model, a patients failure to meet the specified clinical outcome can result in the drug maker having to refund payments received and/or forfeit any subsequent payments.

These new models are also being blended to create payment plans which combine annuity-style payments with rebates and outcomes-dependent instalments. We expect that in the years to come other creative payment models will emerge and be adapted from other therapy areas. For example, in Australia, the government has used a subscription style model that allowed it to pay a lump sum to drug makers for unlimited access for patients to curative hepatitis C treatments such as Sovaldi for a period of time.

Example annuity and outcomes-based reimbursement models for cell and gene therapies:

Licensing challenges

Cell and gene therapies often have their roots in academic research laboratories and the main players in this field of treatments have close ties and valuable licensing agreements with academic research institutions. For example, AveXis, the biotech company that developed Zolgensma, started as a spin-out to continue research conducted at the Center for Gene Therapy at Nationwide Childrens Hospital in Columbus, Ohio. To further its spinal muscular atrophy work, the biotech also licensed a patent owned by Martine Barkats, a researcher at the Institut de Myologie, Paris. Shortly after, AveXis was bought by Novartis for $8.7 billion. Cell and gene therapies such as Zolgensma will generally have more constituent parts (such as promoters, viral vectors and cell lines) than other more conventional small molecule therapies. This means that a party commercialising a cell or gene therapy will often need to license in more third party intellectual property or materials than a manufacturer of a conventional small molecule therapy. Most cell and gene therapies reaching the market are therefore likely to be underpinned by one or more licence agreements.Licensing challenges

While much has been said about the impact of alternative pricing and reimbursement mechanisms on drug makers, payers and patients, we want to also consider the impact on licensors of the intellectual property which enables the development and manufacture of a therapy. In particular, how future pricing and reimbursement models can impact the royalties payable by licensees to their licensors. One inherent challenge is that these licences are generally negotiated many years before the commencement of discussions with payers on pricing and reimbursement mechanisms, making it very difficult to predict which scenarios will be relevant down the line. The positions of all of the stakeholders in the pricing debate are also constantly evolving, especially as data on the cost-effectiveness of annuity and outcomes-based models continues to accumulate. One factor which makes things particularly difficult for licensors in forecasting potential future royalty streams for these products is that a licensor would rarely have any involvement in negotiations regarding pricing and reimbursement so will have no control over the model adopted.

Annuity model challenges

Generally a licensor will only receive royalties once the licensee has itself received (or at least invoiced) payment from payers. An annuity payment model is therefore likely to mean that royalties will also be paid in instalments potentially spread over a number of years following treatment of a patient. While in practice this may not be a large change for licensors to adjust to (as annual payments for these high price treatments are not out of line with other orphan drug costs, most of which need to be taken over a long period of time) there are also other factors to consider.

One concern that has been raised with annuity payment models is that there may be an increased risk of non-payment as over time licensees may face difficulties in collecting payments, for example because a payer stops complying with payment schedules or becomes insolvent. This may have the knock-on effect of reducing royalties due to a licensor. Licensors may seek to reduce this non-payment risk by asking that royalties are payable on sums invoiced by a licensee, rather than sums received (although this is likely to be resisted by a licensee or perhaps only accepted with caveats). Annuity-based models are also typically more complicated and more expensive for a licensee to manage administratively and those costs are likely to be deductible from sales totals before a licensors royalties are calculated.

From a legal drafting perspective, care would also need to be taken by the licensor when defining payment terms and the royalty term (which is commonly linked to patent expiry) to ensure that the licensor continued to receive royalties in respect of patients who are treated within the royalty term, notwithstanding the fact that payment may not be received until after the patents and royalty term has expired.

Outcome-based model challenges

In relation to outcome-based models, a fundamental concern for both licensors and licensees is the uncertainty associated with a model which involves an upfront payment of the full treatment price but a refund payable some months or years down the line if the clinical outcomes are not met.

If royalties are payable on net sales of the therapy on a regular basis (e.g. quarterly or annually) then unless the licence includes a mechanism to take account of outcomes-based refunds made by the licensee to payers, the licensee could find itself out of pocket, unable to recover royalties paid to the licensor despite having had to refund the therapy price to the payer. To counter this risk, a licensee may seek to build in a royalty claw back mechanism into the licence, or to delay the point at which royalties are payable until after the relevant patient has met the required outcome. However, a licensor is unlikely to accept a significant delay in payment of royalties, particularly where the licensee has itself been paid. Academic licensors, with an obligation to invest income from technology transfer activities into research and the provision of education, are particularly unlikely to agree a royalty claw back structure which could force them to refund royalties or milestones a year or more after having received them.

One alternative option may be to agree that the licensee can make deductions against future royalty payments. A further alternative could be for some portion of the royalties paid to be retained in escrow for a period of time, to be released to the licensor upon achievement of a positive clinical outcome or expiry of a set period of time. However, escrow arrangements necessarily increase the complexity of agreements and are difficult to negotiate upfront when payment and reimbursement models and the associated outcome triggers have not yet been set.

A compromise?

As we have outlined in this article, although there are some things each party can consider at the outset of negotiating a licence, getting into protracted negotiations about hypothetical scenarios is unlikely to be attractive to either party.

The parties may wish to adopt an alternative approach of including robust governance provisions in the licence to deal specifically with this issue. For example, establishing a committee comprised of representatives of both parties to oversee and review issues relating to pricing and reimbursement. This may give the licensor a clearer oversight (and potentially input) into decisions which may impact future royalty streams and may present the licensee with an opportunity to propose alternative payment structures to support its desired pricing model. This could be combined with a mechanism for proposing and agreeing amendments to payment provisions in the licence if necessary to accommodate pricing and reimbursement issues which were unforeseen at the outset. Of course the success of such mechanisms will depend on the strength of the relationship between the parties and a combined willingness to work together and potentially compromise. It would also be important to ensure it is clear what happens where the parties cannot agree (e.g. escalation? expert determination? preservation of the status quo?). However, in a future where pricing and reimbursement issues are only likely to become more complex and of key importance to the success of complex treatments such as cell and gene therapies, it will be interesting to see whether this is a route industry explores.

Conclusion

The launch in recent years of a number of advanced cell and gene therapies with blockbuster price tags has heralded a new era for drug pricing and associated payment and reimbursement issues. It is a trend that looks likely to continue if current pipelines can also deliver much anticipated advanced therapies for common conditions. The high prices associated with these products present a myriad of issues however, not only for patients, payers and healthcare providers, but also for the licensors of the underlying intellectual property underpinning such treatments as industry adopts innovative new payment and reimbursement models which may impact on royalty streams.

When negotiating a licence to technology underpinning a cell or gene therapy the parties should consider how less conventional pricing mechanisms may impact the royalty structure. However, while there are some issues licensees and licensors may be able to consider upfront, it is difficult to anticipate the issues that may become relevant at a stage where pricing models have not been set, particularly as there is no one-size-fits-all pricing approach.

We have proposed an increased use of robust governance processes in a licensing relationship as one option to consider. It will also be interesting to see whether any trends emerge in relation to upfront and milestone payments in response to the challenges outlined above. In particular, licensees may push for more back-loaded or performance-related milestone payments to reflect the risks associated with pricing models which take a longer term view of the cost benefits of these types of therapies. We look forward to seeing what innovative approaches licensors and licensees adopt to adapt to these challenges in the years to come.

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Cell and gene therapies - Lexology

Bicoastal startup Kriya Therapeutics to grow gene therapy manufacturing in NC – WRAL Tech Wire

RESEARCH TRIANGLE PARK Theres a new biotech company setting up shop in the Triangle, and its flush with cash and headed up by some big names in the industry.

MeetKriya Therapeutics the brainchild of Dr. Shankar Ramaswamy, former chief business officer for Axovant Gene Therapies; Fraser Wright, co-founder of Sparks Therapeutics; and Roger Jeffs, the former United Therapeutics CEO who has deep rootsinNorth Carolina.

Launched in 2019, the biotech startup has dual headquarters in Durham and Palo Alto, California, and is billing itself as a next-generation gene therapy company focused on designing and developing treatments for highly prevalent and severe chronic conditions, like diabetes and obesity.

Earlier this month, it arrived in a big way after securing $80.5 million in Series A financing during a pandemic.

Its never easy. But itsa really significant pool of capital for us so were thankful to have been able to get it done,Ramaswamy, Kriyas CEO, told NC Biotech in a video interview this week.[Our] investors have a very long term vision of what a next generation gene therapy company could look like, and were very supportive building towards that vision.

Fraser Wright, PhDScientific Co-Founder and Chief Scientific Advisor; Shankar Ramaswamy, MDCo-Founder, Chairman, and CEO; and Nachi Gupta, MD, PhDChief of Staff.

Among the investors: QVT, Dexcel Pharma, Foresite Capital, Bluebird Ventures (associated with Sutter Hill Ventures), Narya Capital, Amplo,Paul Manning, andAsia Alpha. The round followed an initial seed financing led by Transhuman Capital late last year.

Itsis amilestone for the company andsets us up for success to goout and execute on the things that we really want to get done.

Ramaswamy says the company is now ready to scale, and is focused on building out its teams on both coasts.

We expect to grow very quickly both here in the Bay Area and in North Carolina, he said, emphasizing the Triangles importance as its manufacturing hub. That could be dozens of employees [here] in the not so distant future, if not larger over time.

How it will work: co-founders Ramaswamy and Wright will be based in the Bay area along with finance operations and early-stage research.

Meanwhile, in Durham, co-founder Jeffs will lead a team focused on development and manufacturing. It will include Britt Petty, AveXis former head of global manufacturing and Melissa Rhodes, former chief development officer at Altavant Sciences; and Mitch Lower, another Avexis veteran.

I dont view North Carolina as a satellite office.Thats where well be building our internal manufacturing infrastructure to solve for one of the key bottlenecks in gene therapy,which is manufacturing capacity and quality, saidRamaswamy.

Theres a very strong pool of talent in North Carolina, especially in biologics manufacturing. And [our team] has a very strong track record and history of success with biologics manufacturing, and strong experience there as well. So we think its a great place to be, given the past couple of decades, where there have been so many successful products actually manufactured in North Carolina.

Already, Kriyahas a number of gene therapies in the pipeline.

Among them: KT-A112, an investigational gene therapy administered by intramuscular injection that delivers the genes to produce insulin and glucokinase for type 1 and type 2 diabetes;KT-A522, an investigational gene therapy administered by salivary gland injection that delivers the gene to produce a glucagon-like peptide 1 (GLP-1) receptor agonist for type 2 diabetes and severe obesity; andKT-A83, an investigational gene therapy administered by intrapancreatic injection that delivers the gene to produce modified insulin growth factor 1 (IGF-1) for type 1 diabetes.

The team is currently set up in a temporary office in Durham, but plans to move intoamore permanent space somewhere in the Research Triangle in the near future.

Kriya is building a leading team and cutting-edge infrastructure to engineer best-in-class gene therapies for severe chronic conditions and accelerate their advancement into human clinical trials, saidJeffs, its vice chairman. Through its R&D laboratory capabilities in the Bay Area and in-house process development and manufacturing infrastructure inResearch Triangle Park, I believe that Kriya will be uniquely positioned to become a leader in the gene therapy field.

(c) North Carolina Biotechnology Center

Durhams Kriya Therapuetics lands $80M to advance gene therapies for diabetes, severe obesity

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Bicoastal startup Kriya Therapeutics to grow gene therapy manufacturing in NC - WRAL Tech Wire

Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy | DNA RNA and Cells | News Channels – PipelineReview.com

DetailsCategory: DNA RNA and CellsPublished on Tuesday, 26 May 2020 18:08Hits: 457

ATLANTA, GA, USA I May 26, 2020 I Expression Therapeutics has announced that it has received clearance by the United States Food and Drug Administration (FDA) to proceed following review of its Investigational New Drug Application (IND) for clinical testing of its novel lentiviral vector-based gene therapy ET3 for hemophilia A. Hemophilia A is the most common severe congenital bleeding disorder and afflicts approximately 1 in 8,000 people. Without treatment, severe hemophilia is crippling and fatal by late adolescence to early adulthood.

The ET3 gene therapy developed by Expression Therapeutics combines innovative platform technologies in protein bioengineering and tissue-directed expression. ET3 consists of autologous mobilized peripheral blood stem and progenitor cells transduced with a recombinant lentiviral vector, encoding a bioengineered coagulation factor VIII transgene designed for highlevel expression at low vector copy number. In the ET3 trial, subjects will be preconditioned with low-dose stem and immune cell suppressing agents prior to receiving a single infusion of ET3. The high-expression factor VIII can correct the bleeding tendency in hemophilia A. The duration of ET3 activity is expected to be the normal lifetime of the patient. Expression Therapeutics expects to initiate a Phase 1 clinical trial titled ET3-201 at Emory University and enroll patients shortly.

"We are extremely pleased that the FDA has granted permission to proceed with this clinical study," said Trent Spencer, Ph.D., President of Expression Therapeutics and Director of the Cell and Gene Therapy Program in the Aflac Cancer and Blood Disorders Center at Emory University.

Hematopoietic stem and progenitor cell lentiviral gene therapy is currently the only approach that offers the possibility of permanent cure of hemophilia A and provides an opportunity to reach both pediatric and adult populations.

"We are very excited to get the hemophilia A clinical trial underway, the first of six gene therapy products currently under development at Expression Therapeutics," said Mohan Rao, Ph.D., CEO of Expression Therapeutics.

Expression Therapeutics is a biotechnology company based in Atlanta. The current therapeutic pipeline includes advanced gene therapies for hemophilia A and B; neuroblastoma, T-cell leukemia/lymphoma, and acute myeloid leukemia (AML); and primary immunodeficiencies such as hemophagocytic lymphohistiocytosis (HLH).

SOURCE: Expression Therapeutics

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Expression Therapeutics Announces IND Approval by the FDA for Hemophilia A Gene Therapy | DNA RNA and Cells | News Channels - PipelineReview.com

Lab Mice Shed Fat and Build Muscle with Gene Therapy – The Great Courses Daily News

By Jonny Lupsha, News Writer

According to the Fierce Biotech article, the mice who underwent the new gene therapy were injected with a gene that makes the protein follistatin, which in turn blocks a protein called myostatin. Myostatin regulates muscle growth. The therapy caused a significant buildup of muscle mass in the mice while also preventing obesity, the article said. The mice didnt just build muscle; they also nearly doubled their strength without exercising any more than they usually did. Despite being fed a high-fat diet, they had fewer metabolic issues and stronger hearts than did animals that did not receive the follistatin gene.

Scientists have been developing gene therapy for many years. It can change our bodies in many ways, and has potential serving as a treatment for cancer and muscular dystrophy.

The procedure that the mice underwent encapsulates what gene therapy isalthough scientists generally focus on people.

I define [gene therapy] as the addition of genes to humans for medical purposes, said Dr. David Sadava, Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center.

Dr. Sadava said gene therapy is based on four assumptions. First, whoever is doing the gene therapy has to know the gene thats involved in whichever problem needs to be treated. Second, they must have a normal, healthy copy of that gene available in the lab. Third, they must know where and when the gene is normally expressed. Finally, they have to be fairly certain what will happen when the gene is expressed normally.

Additionally, gene therapy must do several things in order to be considered successful.

First, gene therapy must get the gene into the appropriate cells, Dr. Sadava said. Second, gene therapy must get the gene expressed in those cells. Third, we have to get the gene integrated into the genome of the target cells so itll be there permanently. And fourth, you better not have any bad side effects to gene therapy, like any therapy in medicine.

According to Dr. Sadava, one kind of gene therapy is referred to as gene augmentation, and it comes into play when the functional product of a gene has been lost and no longer gets produced normally. By injecting a gene into someone, healthy copies of a protein product will be made and function restored.

We could hypothetically think of muscular dystrophy as a good target for gene therapy, he said. We know that muscles lack the protein dystrophinits an organizing proteinso well put in the good gene for good dystrophin.

Another kind of gene therapy is called target cell killing. Dr. Sadava said it uses a gene that either produces a poison that kills certain types of cells or it stimulates the immune system to do so. Target cell killing can be applied to cancer.

A gene is put into cancer cells that allows them to produce a protein that will make a toxic drug from a harmless chemical, Dr. Sadava said. So the idea is we inject a harmless chemical into the body, it goes all over the body and when it enters a tumor cell, its converted into a poison by the gene product of the gene that weve put in for gene therapy. So we might put in a gene that will cause a protein to be made that attracts killer T cells so the tumor will stick up its hand and say Come kill me now.'

Gene therapy is an exciting field in science and medicine with a lot of potential for humans. For now, it may seem like its just helping some overweight mice get a confidence boost, but the practical applications should shore up within our lifetime.

Dr. David Sadava contributed to this article. Dr. Sadava is Adjunct Professor of Cancer Cell Biology at the City of Hope Medical Center in Duarte, CA, and the Pritzker Family Foundation Professor of Biology, Emeritus, at The Claremont Colleges. Professor Sadava graduated from Carleton University with a B.S. with first-class honors in biology and chemistry. He earned a Ph.D. in Biology from the University of California, San Diego.

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Lab Mice Shed Fat and Build Muscle with Gene Therapy - The Great Courses Daily News

Troubleshooting the Development of New Gene Therapies – Technology Networks

Gene therapy does more than treat genetic diseases it can cure them. A one-time dose of a non-replicative viral vector, such as commonly used recombinant adeno-associated virus (AAV), delivers a functional gene to replace or compensate for a dysfunctional version that is causing a patients disease (Figure 1). As a cutting-edge biopharmaceutical technology, there are multiple gene therapies now FDA approved; with hundreds more in clinical trials, were likely to see many more of these therapies on the market soon.1 However, to keep up with the rapid pace of clinical research, developers are working to streamline the manufacturing and quality control process to improve quality and lower the cost of bringing these important drugs to market.Developers use a multitude of analytical tests to develop gene therapies and optimize their manufacturing process. When developers get aberrant test results, they must be able to interpret where the problem lies. Did the manufacturing process produce an undesirable product, or is the analytical testing method unreliable? Analytical testing companies that have the infrastructure, personnel, and experience often partner with developers to tighten up analytical variability so that results of tests clearly indicate where there are opportunities to increase efficiency and product quality.

Figure 1. Gene delivery by recombinant viral vector.During gene therapy, viral capsids containing the therapeutic gene are taken up by the patients cells and the genetic material is delivered to the nucleus. There, the gene gets expressed as a protein necessary for the patients health. Credit: Avomeen.

Figure 2. A full AAV capsid and associated capsid impurities. Complete viral capsids have AAV are assembled from 60 capsid proteins, with a defined stoichiometry and shape and contain a therapeutic gene. AAV vector impurities include capsids that contain too many copies of the gene (overfilled), those that contain lower copy numbers or truncations of the gene (partially full), or empty capsids that contain no genetic material. Credit:Avomeen.

There are several ways to measure the empty/full capsid ratio, and as developers are establishing their chemistry, manufacturing and control (CMC) protocol, it is important that they choose an optimized method, as they must use that method for effective quality control from early process development to lot release and stability.3 Gene therapy developers may choose analytical ultracentrifugation to evaluate capsids, but while highly effective, this method is not as quantitative, robust or efficient as some newer methods. High-performance liquid chromatography (HPLC) using AAV full/empty analytical columns have been demonstrated to be highly effective at separating full, empty, and improperly filled capsids for robust quantification. Additionally, this method is higher throughput than ultracentrifugation, and requires less precious AAV sample to run.

Cellular potency is evaluated by transducing cells with the AAV product and then measuring a phenotypic or functional outcome due to the transduction. Developing these tests can be challenging because there is no one-size-fits-all test that will give developers the answers they need. Developers often draw on the experience of analytical labs to determine how to best evaluate their AAV products transduction efficiency.A gene therapy in development must also be tested to ensure that it is free of residual, process-related impurities such as polyethylenimine, iodixanol, poloxamer, and other excipients that must be removed in the final product to ensure safety. Few research and manufacturing facilities have the equipment and expertise necessary to perform this kind of testing, and it is advisable to find one that has experience testing polymers, extractables and leachables to examine if components of the manufacturing equipment or drugs packaging are not contaminating the final product.

As fast-paced as the gene therapy field is now, it stands to become a true race to the finish line to bring new gene therapies to market in the near future. Regulatory bodies are becoming more familiar with reviewing gene therapies, and the road to commercialization will move more quickly. There is no denying that gene therapies will bring incredible benefits to patients, but it will be crucial to improve manufacturing efficiency and lower costs to make gene therapies more accessible to the patients who need them.References

1. Colasante, W., Diesel, P., and Gerlovin, Lev. (2018). New Approaches To Market Access And Reimbursement For Gene And Cell Therapies. Cell & Gene. Retrieved from: https://www.cellandgene.com/doc/new-approaches-to-market-access-and-reimbursement-for-gene-and-cell-therapies-0001

2. Fraser Wright, J. (2014). Product-Related Impurities in Clinical-Grade Recombinant AAV Vectors: Characterization and Risk Assessment. Biomedicines, 2, 80-97; doi:10.3390/biomedicines2010080

3. U.S. Food & Drug Administration (2019). Guidance for Human Somatic Cell Therapy and Gene Therapy. Retrieved from: https://www.fda.gov/animal-veterinary/guidance-industry/chemistry-manufacturing-and-controls-cmc-guidances-industry-gfis

4. Stein, R. (2019). At $2.1 Million, New Gene Therapy Is The Most Expensive Drug Ever. NPR. Retrieved from: https://www.npr.org/sections/health-shots/2019/05/24/725404168/at-2-125-million-new-gene-therapy-is-the-most-expensive-drug-ever

5. Cohen, J.T, Chambers, J. D., Silver, M. C., Lin, P., Neumann, P.J. (2019). Putting The Costs And Benefits Of New Gene Therapies Into Perspective. Health Affairs. Retrieved from: https://www.healthaffairs.org/do/10.1377/hblog20190827.553404/full/

6. ATCC (accessed May, 2020) ATCC Virus Reference Materials. Retrieved from: https://www.atcc.org/en/Standards/Standards_Programs/ATCC_Virus_Reference_Materials.aspx#

7. U.S. FDA (2020). FDA Details Policies on Gene Therapies in Seven Guidances. Retrieved from: https://www.fdanews.com/articles/195767-fda-details-policies-on-gene-therapies-in-seven-guidances

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Reversing SHANK3 mutations in mice mitigates autism-like traits – Spectrum

Double dose: Mice with mutations in both copies of SHANK3 have more behavioral differences than animals with mutations in one copy of the gene.

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Correcting a mutation in the autism gene SHANK3 in fetal mice lessens some autism-like behaviors after birth, according to a new study1. The work adds to evidence that gene therapy may help some people with SHANK3 mutations.

In people, mutations in SHANK3 can lead to Phelan-McDermid syndrome, a condition that causes developmental delays and often autism. Up to 2 percent of people with autism have a mutation in SHANK32.

Our findings imply that early genetic correction of SHANK3 has the potential to provide therapeutic benefit for patients, lead investigator Craig Powell, professor of neurobiology at the University of Alabama at Birmingham, wrote in an email.

A 2016 study showed that correcting mutations in SHANK3 in both young and adult mice can decrease excessive grooming, which is thought to correspond to repetitive behaviors in people with autism.

Last year, Powell and his team also showed that correcting SHANK3 mutations in adult mice eliminates some autism-like behaviors3. But the results were difficult to interpret. The team reversed the mutation using an enzyme called Cre-recombinase that could edit SHANK3 if the animals were given a drug called tamoxifen. Control mice in that study that did not receive tamoxifen but had the gene for Cre still showed behavior changes, raising the possibility that the enzyme affected their brains.

In the new work, Powells team used a different approach. They engineered mice with a mutation in both or only one copy of SHANK3 the latter more closely mirrors what happens in people. Some animals had the Cre gene, but some also had another gene for a Cre-activating protein that is naturally expressed when the animals are in utero. By using this protein, the researchers could avoid using tamoxifen, which some studies have shown may also cause behavioral changes in mice4.

The control mice had either the gene for Cre-recombinase or fortheCre-activating protein, but not both, allowing the researchers to isolate any effects from the method itself.

They found that correcting the mutation lowers some but not all of the animals autism-like behaviors, a finding Powell says is surprising. The mice groom less and are more social by some measures, but they still prefer interacting with an object than with another mouse.

We dont really know why some behaviors are affected and not others, Powell says.

Mice with one mutated copy of SHANK3 have fewer behavioral differences than mice with two, they also found, which indicates the value of using both kinds of animals in gene-reversal studies, experts say.

The fact that they did analyze both side by side, and they did see some differences, I find quite intriguing, says Gaia Novarino, professor of neuroscience at the Institute of Science and Technology in Klosterneuburg, Austria.

The team originally planned to consider when and where in the brain SHANK3 was corrected. But the Cre-activating protein involved in the study was expressed throughout the brain, preventing region-specific findings.

The team gave some mice the antibiotic doxycycline to suppress Cre expression, in hopes of also testing the effects of correcting SHANK3 in adulthood. But the method failed, for unknown reasons.

It is also important to publish experiments that do not work out exactly as planned, Powell says.

The teams openness about the studys shortcomings could help others design their own studies or re-evaluate previous work, says Yong-Hui Jiang, chief of medical genetics at Yale University.

People will learn from the difficulties and the experience, Jiang says.

It would still be helpful to test whether correcting SHANK3 mutations can reverse autism-like behaviors in adult mice without using tamoxifen, other researchers say.

Its beneficial to do experiments in such a way where you leave very little room for alternative interpretations, says Gavin Rumbaugh, professor of neuroscience at the Scripps Research Institute in Jupiter, Florida. He suggests using a mouse that does not express Cre until the animal is administered doxycycline, rather than trying to suppress Cre with the drug.

The work lends credence to the idea that gene therapy might alleviate some difficulties associated with autism in people with SHANK3 mutations, researchers say. Further studies could also investigate in how many cells the gene needs to be restored to change behavior, and what would be the safest and most effective stage of development to intervene with a gene therapy.

The impression is you have a quite large window, Novarino says. Thats quite positive.

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Reversing SHANK3 mutations in mice mitigates autism-like traits - Spectrum

Orchard Therapeutics to Present at Virtual Investor Conferences in June – Yahoo Finance UK

BOSTON and LONDON, May 27, 2020 (GLOBE NEWSWIRE) -- Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that presentations by the management team will be made at the following investor conferences in June:

Live webcasts of the presentations will be available under "News & Events" in the Investors & Media section of the company's website at http://www.orchard-tx.com. Webcast replays will be archived on the Orchard website following the presentation.

About OrchardOrchard Therapeuticsis a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Ourex vivoautologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy inMilan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters inLondonandU.S.headquarters inBoston. For more information, please visitwww.orchard-tx.com, and follow us onTwitterandLinkedIn.

Availability of Other Information About OrchardInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (twitter.com/orchard_txandwww.linkedin.com/company/orchard-therapeutics), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

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Orchard Therapeutics to Present at Virtual Investor Conferences in June - Yahoo Finance UK

Gene Therapy market worldwide is projected to grow by US$3.3 Billion – GlobeNewswire

New York, May 22, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global Gene Therapy Industry" - https://www.reportlinker.com/p05817594/?utm_source=GNW Poised to reach over US$125.3 Million by the year 2025, Lentivirus will bring in healthy gains adding significant momentum to global growth.

- Representing the developed world, the United States will maintain a 30% growth momentum. Within Europe, which continues to remain an important element in the world economy, Germany will add over US$133.3 Million to the regions size and clout in the next 5 to 6 years. Over US$117.2 Million worth of projected demand in the region will come from Rest of Europe markets. In Japan, Lentivirus will reach a market size of US$6.5 Million by the close of the analysis period. As the worlds second largest economy and the new game changer in global markets, China exhibits the potential to grow at 39.2% over the next couple of years and add approximately US$797 Million in terms of addressable opportunity for the picking by aspiring businesses and their astute leaders. Presented in visually rich graphics are these and many more need-to-know quantitative data important in ensuring quality of strategy decisions, be it entry into new markets or allocation of resources within a portfolio. Several macroeconomic factors and internal market forces will shape growth and development of demand patterns in emerging countries in Asia-Pacific, Latin America and the Middle East. All research viewpoints presented are based on validated engagements from influencers in the market, whose opinions supersede all other research methodologies.

Read the full report: https://www.reportlinker.com/p05817594/?utm_source=GNW

GENE THERAPY MCP-1MARKET ANALYSIS, TRENDS, AND FORECASTS, MAY 2CONTENTS

I. INTRODUCTION, METHODOLOGY & REPORT SCOPE

II. EXECUTIVE SUMMARY

1. MARKET OVERVIEW Global Competitor Market Shares Gene Therapy Competitor Market Share Scenario Worldwide (in %): 2019 & 2028 Impact of Covid-19 and a Looming Global Recession 2. FOCUS ON SELECT PLAYERS 3. MARKET TRENDS & DRIVERS 4. GLOBAL MARKET PERSPECTIVE Table 1: Gene Therapy Global Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 2: Gene Therapy Global Retrospective Market Scenario in US$ Thousand by Region/Country: 2012-2019 Table 3: Gene Therapy Market Share Shift across Key Geographies Worldwide: 2012 VS 2020 VS 2027 Table 4: Lentivirus (Vector) World Market by Region/Country in US$ Thousand: 2020 to 2027 Table 5: Lentivirus (Vector) Historic Market Analysis by Region/Country in US$ Thousand: 2012 to 2019 Table 6: Lentivirus (Vector) Market Share Breakdown of Worldwide Sales by Region/Country: 2012 VS 2020 VS 2027 Table 7: AAV (Vector) Potential Growth Markets Worldwide in US$ Thousand: 2020 to 2027 Table 8: AAV (Vector) Historic Market Perspective by Region/Country in US$ Thousand: 2012 to 2019 Table 9: AAV (Vector) Market Sales Breakdown by Region/Country in Percentage: 2012 VS 2020 VS 2027 Table 10: RetroVirus & Gamma RetroVirus (Vector) Geographic Market Spread Worldwide in US$ Thousand: 2020 to 2027 Table 11: RetroVirus & Gamma RetroVirus (Vector) Region Wise Breakdown of Global Historic Demand in US$ Thousand: 2012 to 2019 Table 12: RetroVirus & Gamma RetroVirus (Vector) Market Share Distribution in Percentage by Region/Country: 2012 VS 2020 VS 2027 Table 13: Modified Herpes Simplex Virus (Vector) World Market Estimates and Forecasts by Region/Country in US$ Thousand: 2to 2027 Table 14: Modified Herpes Simplex Virus (Vector) Market Historic Review by Region/Country in US$ Thousand: 2012 to 2019 Table 15: Modified Herpes Simplex Virus (Vector) Market Share Breakdown by Region/Country: 2012 VS 2020 VS 2027 Table 16: Adenovirus (Vector) World Market by Region/Country in US$ Thousand: 2020 to 2027 Table 17: Adenovirus (Vector) Historic Market Analysis by Region/Country in US$ Thousand: 2012 to 2019 Table 18: Adenovirus (Vector) Market Share Distribution in Percentage by Region/Country: 2012 VS 2020 VS 2027 Table 19: Other Applications (Vector) World Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020 to 2027 Table 20: Other Applications (Vector) Market Worldwide Historic Review by Region/Country in US$ Thousand: 2012 to 2019 Table 21: Other Applications (Vector) Market Percentage Share Distribution by Region/Country: 2012 VS 2020 VS 2027 III. MARKET ANALYSIS GEOGRAPHIC MARKET ANALYSIS UNITED STATES Market Facts & Figures US Gene Therapy Market Share (in %) by Company: 2019 & 2025 Market Analytics Table 22: United States Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 23: Gene Therapy Market in the United States by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 24: United States Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 CANADA Table 25: Canadian Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 26: Canadian Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 27: Gene Therapy Market in Canada: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 JAPAN Table 28: Japanese Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 29: Gene Therapy Market in Japan: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 30: Japanese Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 CHINA Table 31: Chinese Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 32: Gene Therapy Historic Market Analysis in China in US$ Thousand by Vector: 2012-2019 Table 33: Chinese Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 EUROPE Market Facts & Figures European Gene Therapy Market: Competitor Market Share Scenario (in %) for 2019 & 2025 Market Analytics Table 34: European Gene Therapy Market Demand Scenario in US$ Thousand by Region/Country: 2020-2027 Table 35: Gene Therapy Market in Europe: A Historic Market Perspective in US$ Thousand by Region/Country for the Period 2012-2019 Table 36: European Gene Therapy Market Share Shift by Region/Country: 2012 VS 2020 VS 2027 Table 37: European Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 38: Gene Therapy Market in Europe in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 39: European Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 FRANCE Table 40: Gene Therapy Market in France by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 41: French Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 42: French Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 GERMANY Table 43: Gene Therapy Market in Germany: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 44: German Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 45: German Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 ITALY Table 46: Italian Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 47: Gene Therapy Historic Market Analysis in Italy in US$ Thousand by Vector: 2012-2019 Table 48: Italian Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 UNITED KINGDOM Table 49: United Kingdom Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 50: Gene Therapy Market in the United Kingdom: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 51: United Kingdom Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 SPAIN Table 52: Spanish Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 53: Spanish Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 54: Gene Therapy Market in Spain: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 RUSSIA Table 55: Russian Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 56: Gene Therapy Market in Russia by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 57: Russian Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 REST OF EUROPE Table 58: Rest of Europe Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 59: Gene Therapy Market in Rest of Europe in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 60: Rest of Europe Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 ASIA-PACIFIC Table 61: Asia-Pacific Gene Therapy Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 62: Gene Therapy Market in Asia-Pacific: Historic Market Analysis in US$ Thousand by Region/Country for the Period 2012-2019 Table 63: Asia-Pacific Gene Therapy Market Share Analysis by Region/Country: 2012 VS 2020 VS 2027 Table 64: Gene Therapy Market in Asia-Pacific by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 65: Asia-Pacific Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 66: Asia-Pacific Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 AUSTRALIA Table 67: Gene Therapy Market in Australia: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 68: Australian Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 69: Australian Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 INDIA Table 70: Indian Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 71: Indian Gene Therapy Historic Market Review by Vector in US$ Thousand: 2012-2019 Table 72: Gene Therapy Market in India: Percentage Share Breakdown of Sales by Vector for 2012, 2020, and 2027 SOUTH KOREA Table 73: Gene Therapy Market in South Korea: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 74: South Korean Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 75: Gene Therapy Market Share Distribution in South Korea by Vector: 2012 VS 2020 VS 2027 REST OF ASIA-PACIFIC Table 76: Rest of Asia-Pacific Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 77: Gene Therapy Market in Rest of Asia-Pacific: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 78: Rest of Asia-Pacific Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 LATIN AMERICA Table 79: Latin American Gene Therapy Market Trends by Region/Country in US$ Thousand: 2020-2027 Table 80: Gene Therapy Market in Latin America in US$ Thousand by Region/Country: A Historic Perspective for the Period 2012-2019 Table 81: Latin American Gene Therapy Market Percentage Breakdown of Sales by Region/Country: 2012, 2020, and 2027 Table 82: Latin American Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 83: Gene Therapy Historic Market Analysis in Latin America in US$ Thousand by Vector: 2012-2019 Table 84: Latin American Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 ARGENTINA Table 85: Argentinean Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 86: Gene Therapy Market in Argentina in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 87: Argentinean Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 BRAZIL Table 88: Gene Therapy Market in Brazil by Vector: Estimates and Projections in US$ Thousand for the Period 2020-2027 Table 89: Brazilian Gene Therapy Historic Market Scenario in US$ Thousand by Vector: 2012-2019 Table 90: Brazilian Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 MEXICO Table 91: Gene Therapy Market in Mexico: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 92: Mexican Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 93: Mexican Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 REST OF LATIN AMERICA Table 94: Rest of Latin America Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 95: Gene Therapy Market in Rest of Latin America by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 96: Rest of Latin America Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 MIDDLE EAST Table 97: The Middle East Gene Therapy Market Estimates and Forecasts in US$ Thousand by Region/Country: 2020-2027 Table 98: Gene Therapy Market in the Middle East by Region/Country in US$ Thousand: 2012-2019 Table 99: The Middle East Gene Therapy Market Share Breakdown by Region/Country: 2012, 2020, and 2027 Table 100: The Middle East Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020 to 2027 Table 101: The Middle East Gene Therapy Historic Market by Vector in US$ Thousand: 2012-2019 Table 102: Gene Therapy Market in the Middle East: Percentage Share Breakdown of Sales by Vector for 2012,2020, and 2027 IRAN Table 103: Iranian Market for Gene Therapy: Annual Sales Estimates and Projections in US$ Thousand by Vector for the Period 2020-2027 Table 104: Gene Therapy Market in Iran: Historic Sales Analysis in US$ Thousand by Vector for the Period 2012-2019 Table 105: Iranian Gene Therapy Market Share Analysis by Vector: 2012 VS 2020 VS 2027 ISRAEL Table 106: Israeli Gene Therapy Market Estimates and Forecasts in US$ Thousand by Vector: 2020-2027 Table 107: Gene Therapy Market in Israel in US$ Thousand by Vector: A Historic Review for the Period 2012-2019 Table 108: Israeli Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 SAUDI ARABIA Table 109: Saudi Arabian Gene Therapy Market Growth Prospects in US$ Thousand by Vector for the Period 2020-2027 Table 110: Gene Therapy Historic Market Analysis in Saudi Arabia in US$ Thousand by Vector: 2012-2019 Table 111: Saudi Arabian Gene Therapy Market by Vector: Percentage Breakdown of Sales for 2012, 2020, and 2027 UNITED ARAB EMIRATES Table 112: Gene Therapy Market in the United Arab Emirates: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 113: United Arab Emirates Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 114: Gene Therapy Market Share Distribution in United Arab Emirates by Vector: 2012 VS 2020 VS 2027 REST OF MIDDLE EAST Table 115: Gene Therapy Market in Rest of Middle East: Recent Past, Current and Future Analysis in US$ Thousand by Vector for the Period 2020-2027 Table 116: Rest of Middle East Gene Therapy Historic Market Analysis in US$ Thousand by Vector: 2012-2019 Table 117: Rest of Middle East Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 AFRICA Table 118: African Gene Therapy Market Estimates and Projections in US$ Thousand by Vector: 2020 to 2027 Table 119: Gene Therapy Market in Africa by Vector: A Historic Review in US$ Thousand for 2012-2019 Table 120: African Gene Therapy Market Share Breakdown by Vector: 2012 VS 2020 VS 2027 IV. COMPETITION

Total Companies Profiled: 98 Read the full report: https://www.reportlinker.com/p05817594/?utm_source=GNW

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Gene Therapy market worldwide is projected to grow by US$3.3 Billion - GlobeNewswire

Bankruptcy – Nolo’s Free Legal Encyclopedia | Nolo

When bills become unmanageable, such as after a divorce, illness, or job loss, bankruptcy provides a filer with a financial safety net. It works by wiping out ordischarging qualifying debtcredit card balances, overdue utility bills, personal loans, gym memberships, and moreand giving the filer a fresh start. If youreconsidering filing for bankruptcy, youll want to learnwhat each chapter can and cannot do.

Individuals oftenfile for Chapter 7 bankruptcybecause its quick and doesnt require debtors to repay creditors. Higher-income earners who make too much for a Chapter 7 discharge canfile for Chapter 13 bankruptcy. Although a debtor must pay back some amount through a Chapter 13 repayment plan, Chapter 13 has other benefits, like preventing a home foreclosure or car repossession and reducing the amount owed on secured debt. Both bankruptcy chaptersstop harassing debt collectorsand put an end to wage garnishments, creditor lawsuits, and other collection actions.

Filing forbankruptcy will affect your credit score, but it will improve with timeand often far sooner than most filers expect. In fact, many people find that filing for bankruptcy repairs credit faster than would be possible otherwise.

Bankruptcy isnt just for individuals with consumer debt problems. Filing can benefit asmall business owner by minimizing personal liabilityafter a company closure or by helping a small business return to profitability.

Finally, no one wants to file for bankruptcy. If youneed bankruptcy helpbut have reservations, youre not alone. Not only have employerslaid off staggering numbers of workers due to the coronavirus outbreak, but companies large and small are closing at a record paceandmany businesses will seek bankruptcy relief. But thats not as bleak as it might seem. Each fresh startincluding yoursmoves the economy one step closer toward recovery.

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Bankruptcy - Nolo's Free Legal Encyclopedia | Nolo

Hertz, JCPenney, JCrew join list of businesses filing bankruptcy – NBCNews.com

WASHINGTON When the history of the COVID-19 pandemic is written, there will be more than a few words devoted to the retailers the virus decimated as it pounded the economy. The last month, in particular, has brought bankruptcies from well-known brands with deep roots around the country. This weekend, Hertz, the rental car giant, joined the list.

But the impacts of the coronavirus are only half the story. In some cases, such as restaurants and travel companies, the virus is undoubtedly the primary cause of trouble, but in others it looks more like an accelerant gas on a retail fire that has been burning for quite some time.

The last month has been particularly noteworthy. In the space of just two weeks, some of the best-known brands in America declared they were entering Chapter 11 bankruptcy and closing outlets across the country.

Back on May 4, Golds Gym, the national chain of exercise facilities, announced it was headed to Chapter 11, a move affecting roughly 4,000 employees and 700 locations in more than 20 states. The company said it was planning to permanently shutter 30 locations. And J. Crew, the well-known purveyor of preppy attire, also filed for Chapter 11, a move affecting 500 locations and 13,000 employees in 44 states.

On May 7, Neiman Marcus said it was entering Chapter 11, directly affecting roughly 13,000 employees at 68 stores in 18 states. And on May 14, JC Penney, the long-beleaguered legacy retail giant with 850 stores in 49 states said the same thing, a move affecting some 90,000 employees.

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Those are some well-known names, but in some ways their bankruptcies may not be shocking. Gyms and clothing stores are exactly the kinds of businesses that the coronavirus lockdown seems designed to damage. Raising ones heart rate and sweating are at-home activities these days and apparel shopping is done with a few clicks of a mouse.

But even before May, there were signs of trouble for the brick-and-mortar commerce world this year.

Back in mid-February, Pier One entered Chapter 11, a move that affected roughly 970 locations and 18,000 employees scattered around the United States with some in Canada. Art Van Furniture, said it would be shuttering on March 8, affecting 3,000 employees and 169 locations around the Midwest. And on March 11, Modells, which claimed to be the oldest sporting goods store in America said it was entering Chapter 11, closing the doors of about 140 locations with 3,600 employees on the East Coast.

And even beyond retail, there were signs of trouble elsewhere in the economy. In January, Bar Louie, the trendy upscale chain of bar/bistros, announced it would begin a bankruptcy restructuring hitting 90 locations and 1,500 employees.

In other words, even before the COVID-19 pandemic hit the United States, there were signs that 2020 might not be shaping up to be a great year for merchants with real-world physical locations. Part of that may have been economic exhaustion. The post-Great Recession expansion had been unfolding for more than 10 years (since 2009) when 2020 arrived. Some retrenching may have been inevitable.

But on the retail side there was also the steady march of e-commerce, which has been battering brick-and-mortar stores especially hard for a decade now. Consider the numbers from recent years.

In 2018, retailers closed nearly 6,000 brick-and-mortar locations permanently, according to Coresight Research. In 2019, the figure was even higher, 9,300 locations were shuttered. And, of course, all of those closures had nothing to do with the coronavirus pandemic.

For months now, much of the COVID conversation has centered on how the pandemic might change the nation. How deep will the changes be? What will the post-pandemic United States look like, particularly economically?

But even before the virus, the nation and its economy were going through major changes. Keep in mind all those closures in 2018 and 2019 came as the economy was booming.

There is no question that the coronavirus is hammering the U.S. economy and that it is taking a toll on some healthy businesses and employers. But the biggest economic impact from COVID-19 may be that it is pushing the economy into the future much faster than before, striking hard at businesses that were already weak from other challenges.

It all serves as a reminder that even after the pandemic is controlled, the road back to normal is not going to be easy, and normal may look very different.

Dante Chinni

Dante Chinni is a contributor to NBC News specializing in data analysis around campaigns, politics and culture.

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Hertz, JCPenney, JCrew join list of businesses filing bankruptcy - NBCNews.com

Texas bankruptcies are up, and Houston is the epicenter – Houston Chronicle

The list is growing: J.C. Penney, Neiman Marcus, Diamond Offshore Drilling, Alta Mesa Resources, Echo Energy, Alta Petroleum, TriPoint Oilfield Services, Sheridan Holding and Stage Stores.

More Texas businesses are filing for bankruptcy this year than during the Great Recession or anytime in the past two decades, and legal experts said the wave of insolvencies and restructurings is still far from breaking or hitting their peak.

Between Jan. 1 and May 5, more than 545 Texas companies filed for protection from creditors under Chapter 11 of the U.S. Bankruptcy Code up from 234 such filings during the same period in 2019, a 133 percent jump, according to new data provided exclusively to The Texas Lawbook by Androvett Legal Media & Marketing.

ENERGY CARNAGE: More than 240 U.S. energy bankruptcies forecast by 2021

And bankruptcy courts in the Southern District of Texas specifically Houston are the epicenter for the historic number of corporate restructurings expected to be filed this year. So far in 2020, five times more business bankruptcies have been filed in Houston than in any of the other three federal district courts in the state. The Northern District of Texas is a distant second.

There is a tsunami coming, said Foley bankruptcy partner Holly ONeil. For tens of thousands of retailers and restaurants and other businesses, their incoming revenue completely stopped, but their expenses kept coming. The options for many of these businesses are running out.

The Androvett data show that an average of 32 Texas companies has filed to restructure each week this year, compared with an average of 13 companies a week last year and 23 corporate bankruptcies each week in the first half of 2017, which was the previous high in the state.

If you are a restructuring lawyer, you are going to be very busy, said Lou Strubeck, head of the bankruptcy and restructuring practice at Norton Rose Fulbright. Oil and gas and the retail sector had a whole lot of stress even before COVID-19. The only surprising thing is that we havent seen the explosion of bankruptcy filings already. But they are still coming.

Several other prominent companies including CEC Entertainment and Chesapeake Energy are reportedly preparing bankruptcy filings.

I expect the volume will go up significantly. We are in the early stages, said Duston McFaul, a partner at Sidley Austin in Houston. This has the makings to be a long, several-year cycle with widespread imbalances to address.

The surge of bankruptcies by small-business owners also has been delayed because the stay-at-home orders have prevented owners from finding and meeting with lawyers to handle their filings.

Creditors are being patient with retailers and restaurants, at least for a short time, according to McFaul.

Lessors are not rushing to push out distressed businesses because theres currently no one lined up to replace tenants, he said. A strained revenue stream is better than none at all.

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The same is true in the oil industry, except that energy company restructurings tend to be significantly more complicated because there are so many parties and because the price of oil continues to be unstable.

Lenders arent going to be too aggressive in forcing energy companies into court to reorganize, Strubeck said, because they dont know what they would do with the assets and they dont want to run these companies.

The big question is, will private equity jump in or are they gun-shy about oil and gas? said Bill Wallander, a partner at Houston-based Vinson & Elkins.

Matthew Cavenaugh, a bankruptcy partner with Jackson Walker in Houston, said the answer to that question is a reason why courts may have seen fewer prepackaged bankruptcies and more free fall bankruptcies.

In 2015 and 2016, there was a lot of capital waiting to invest, which was important for exiting bankruptcy, he said. Right now, theres not a lot of access to capital.

Cavenaugh said there is another underlying factor that needs to be considered.

Theres been so much money pumped into the system by the feds, he said. Theres no way to know the impact.

For a longer version of this article, please visit TexasLawbook.net.

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Texas bankruptcies are up, and Houston is the epicenter - Houston Chronicle

Tuesday Morning will close some Idaho stores in bankruptcy – boisedev.com

Tuesday Morning declared bankruptcy Wednesday morning. The off-price home decor store filed court proceedings, telling a judge its struggles before the pandemic hit only grew worse in recent months.

The company says it hopes to stay in business, but will close nearly a third of its locations this summer. Tuesday Morning currently operates five stores in Idaho, and two in Boise.

[Penneys, Pier 1, Gordmans & more: chains shutter some stores what we know now about local outlets]

According to bankruptcy documents reviewed by BoiseDev, two of those stores will close in the first wave. Store locations in Pocatello and Idaho Falls will close, starting as early as June 1. The company and its debtors said they looked at store profitability, sales trends, geography and the possibility of renegotiating leases as factors in the stores it chose to close.

The first wave includes 133 locations. Two stores in Boise, on Boise Ave. at Apple St., and on Milwaukee St. will remain open. Tuesday Morning did say in filings that up to 100 additional stores could close depending on attempts to renegotiate lease agreements.

Tuesday Morning joins other retailers like Pier 1, JCPenney, Neiman Marcus, and J Crew in bankruptcy court in the wake of the pandemic. So far, just Pier 1 announced it would totally shut down, including its Boise locations.

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Tuesday Morning will close some Idaho stores in bankruptcy - boisedev.com

Related Chairman Stephen Ross: Expect a ‘flood’ of retail bankruptcies because of the pandemic – CNBC

Related Cos. Chairman Stephen Ross said the hotel and retail industries are being hit the hardest by the coronavirus pandemic, as travel has been dramatically curtailed and retail businesses have been forced to close up shop.

The crisis will force many retailers into bankruptcy, he said. That would add to a number of them, including department store chains Neiman Marcus, J.C. Penney and Stage Stores, and apparel maker J.Crew, that have already filed.

"You are going to have such a flood of cases going to the bankruptcy court," Ross told CNBC Tuesday morning during an interview on "Squawk Box."

"And these aren't really the type of bankruptcies that were induced by bad practices," he said. "It's really all driven by the pandemic."

In addition to malls and shopping centers, Related owns residential and office space across the U.S. In New York City, it operates the glitzy Hudson Yards mall and the Shops at Columbus Circle both of which remain shuttered as the city, the hardest hit in the nation, continues to employ drastic measures meant to curb the spread of the virus. Hudson Yards, notably, is anchored by the now-bankrupt Neiman Marcus.

Ross added he is most concerned about small business owners in the retail and restaurant business not being able to turn their lights back on. "Many of them probably don't have the wherewithal to reopen," he said.

The retail bankruptcy filings also threaten thousands of more workers in an economy that has already suffered tens of millions of lost jobs.

Meantime, Related's CEO, Jeff Blau, recently told CNBCthat many of the company's retail tenants had been deferring rent payments, as they try to work through the crisis.

By mid-April, he said Related had collected about 35% of April rents from its retail tenants overall. In its enclosed shopping malls, only about 20% of rent checks had come in, Blau said at the time.

Retail real estate landlords such as Simon, Brookfield and Macerich have been grappling with how to operate their businesses when rent is not being paid on time.

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Related Chairman Stephen Ross: Expect a 'flood' of retail bankruptcies because of the pandemic - CNBC