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Category Archives: Transhuman News

Will The Tesla Cybertruck Have Futuristic Curved Windows? – CleanTechnica

Posted: August 22, 2021 at 4:13 pm

A new patent filed by Tesla suggests that the Cybertrick may have some futuristic curved windows that are also durable. The patent was filed with the U.S. Patent and Trademark Office earlier this month and covers windows with curves and feature lines. The patent filing also included a method for manufacturing them.

The production method described in the patent involves applying localized heat from a laser or heating element to a location of a substantially planar glass structure (the glass window, in essence) and bending it at the location to form the feature line. The radius of curvature is a range between 2 millimeters and 5 centimeters. Also, layers of curved or joined glass layers can be added to create a curved multi-layered glass structure.

In the description, Tesla already reminded us that this is possible, since windshields exist. However, the processes for creating windshields starts with a flat sheet of glass that is cut into specific dimensions and heated in an oven to the right temperature, at which point they can be slightly bent or curved into the desired shape. This process is limited by just how much bending or curving you can do with the glass. An example of this is that only smooth, high radius curvatures (13 meters or more) are used for automotive glass structures. With this new patent, Tesla is changing this.

Theres a chance that Tesla may use this new method of making automotive glass for some of the interior elements of the Cybertruck, such as the dash, the front portion of the interior, or in the gauges, displays, and inside panels for doors. Even the consoles could be made from this new glass.

We dont know for sure yet if Tesla will even use this glass (I think it will, but many patents are filed for things that never make it into commercial products). But its exciting to think about, and the patent gives us another clue as to how the Cybertruck may look when its finally ready.

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The Army Plans To Build Balloons That Can Jam Communications From Above – Futurism

Posted: at 4:13 pm

Lone Starr strikes again.Space Jam

The US Army recently unveiled plans to develop, test, and deploy high-altitude systems that can fly over other countries to surveil them and jam enemy communications from up on high.

The system doesnt quite reach space (unless you adhere to the same definition of space as Jeff Bezos or Richard Branson). Instead, the High-Altitude Extended-Range Long Endurance Intelligence Observation system (HELEIOS) would be a network of balloons or solar glide vehicles that can hover at least 60,000 feet off the ground. The upcoming electronic warfare tools dont quite broach the thorny subject of the increasing military weaponization of space but only in the most literal interpretations of what the Army has planned. Because, make no mistake: This is a weapon of a certain stripe.

HELEIOS may not be a spy satellite, but it sure operates like one. With the balloons in place, the Army would be able to monitor, intercept, and block enemy communications. We know, its not as exciting as a laser battle where potential orbital warfare is concerned. But: The ability to jam signals could be key to battle (if not devastating for some) in a future where orbital communications networks are essential for military success.

The idea is blanketing the deep area with low-cost attritable sensors to enable deep sensing and deep effects, Col. Daniel Holland, the Army capability manager for electronic warfare, explained at a Tuesday presentation attended by C4ISRNET. Essentially our question is can we get the payload light enough to fly on this penetrating, high-altitude, attributable platform, get close enough to place our effects on target, likely with a special purpose electronic attack or RF-enabled cyber.

Based on Hollands comments, it seems that technical and logistical issues like figuring out how to control a free-floating balloon are currently holding the Army back from deploying HELEIOS. Issues like is it a good idea to put cyber warfare balloons in the sky? or what will any other country think about this? dont seem to be on the list of concerns, though.

Of course, its an impressive technological feat to add a sophisticated payload to a balloon, then, use it to bring down digital communications. But if nothing else, it reinforces the idea that space (or at least: high-altitude airspace) has undeniably become militarized for the foreseeable future.

READ MORE: U.S. Army wants a high-altitude jammer [C4ISRNET]

More on the militarization of space: Air Force research Lab Says Force Fields Are on the Horizon

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Taco Bell Previewed Its Futuristic Drive-Thru Concept And It’s Absolutely Incredible – Delish

Posted: at 4:13 pm

Taco Bell is no stranger to rolling out innovative food items (they have Loaded Nacho Fries for crying out loud!), but the new drive-thru concept they're proposing just might take the cake. While the next generation of innovations for restaurants like Panera and Pizza Hut are applaudable in their own rights, Taco Bell has a vision that just might change they way we do fast food.

Aptly titling the experience Taco Bell Defy, the new designwhich is scheduled to open in Brooklyn Park, MN, summer 2022will feature a two-story building and a much faster way to get your TB fix. The innovative restaurant will also include a four-lane drive-thru concept with three of those lanes strictly dedicated to mobile and/or delivery order pickups.

Along with the extra lanes, the new 3,000 square-foot restaurant will allow those who order on the mobile app to have a digital check-in screen and scan their order via a unique QR code. That's not the exciting part though. When customers pull forward to get their order, they'll be able to receive their meal through a proprietary lift system and interact with team members via a two-way audio and video experience. Talk about reaching new heights!

Though I'm sure we can expect to hear much more about the new restaurant closer to its opening date, we'll just have to live off the excitement that they've teased us with so far for now. Here's looking forward to seeing more Defy locations throughout the nation in the future!

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Massive Asteroid That Could Obliterate Earth to Fly By, Case the Joint – Futurism

Posted: at 4:13 pm

That WHOOSH you'll feel this weekend is Earth not being obliterated.Rock On

Even though we havent had too many truly near misses, let Asteroid 2016 AJ193 (as its technically known) serve as reason to reevaluate all of your life choices this weekend.

Itll be taking a (relatively) very near fly-by of our planet, casing the place, looking mean, and then. moving on to the rest of the solar system. Even though its officially classified as potentially hazardous thanks to its close proximity to the planet, it doesnt stand a chance of obliterating us, although it will come pretty, pretty close.

Per IFL science, Asteroid 2016 AJ193 named as such for when it was first spotted (in 2016) by the Haleakala Observatorys Panoramic Survey Telescope and Rapid Response System (Pan-STARRS) facility, located in Hawaii will cruise by on Saturday at a distance of 2.1 million miles. That may not sound like much, but the observatory team notes its the closest approach for several decades. Per the raw Jet Propulsion Lab data (which you can view here), IFL points out that AJ193 is 8.9 times the distance between the Earth and the Moon.

This on its own would be pretty fascinating, but the thing is an absoluteunit to boot. Its size has been compared to the Burj Khalifia, the Empire State Building (which its three times the size of), and the Eiffel Tower (which its four times the size of), the Pentagon, a mountain you get the idea. The thing ishuge.

Of course, every time Earth has a close encounter with a rock spiraling by our airspace, its not unreasonable to ask what the hell wed do if, in fact, one of these things cruised our way. Dont worry: There are people working on this very problem. The answer is not nuke it as they do in Michael Bays seminal astro-geology cinematic masterpiece Armageddon, but thats not entirely off-track. NASAs been cooking on a project they call DART: the Double Asteroid Redirection Test.

Basically, DART aims to see if kinetic impactor technology (or: flying a small spaceship into an asteroid to move it off course) would work. That said, a recent hypothetical had some bad news to deliver: Wed be screwed, and in the test, Europe wouldve gotten obliterated (and then, a laArmageddon, we wouldve tried to nuke it, go figure). Either way, asteroid detection and deflection tech remains relatively important: Assuming theres still a habitable planet to destroy by then, an oncoming asteroid set to roll by in 2068 thats coming uncomfortably close is all the more reason detection of these fly-bys remains crucial to developing. Also, the nukes. Apparently, we gotta keep those around, too.

READ MORE: Asteroid As Large As A Mountain Will Fly Near Earth This Weekend [IFL Science]

More on death rocks from space: Theres a Chance This Giant Asteroid Will Smash Earth in 2068

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Scientists Are On the Edge of a Fusion Power Breakthrough – Futurism

Posted: at 4:13 pm

Fusion energy to many, the holy grail of sustainable energy is on the edge of its next breakthrough.

Using a powerful laser at the National Ignition Facility (NIF) in California, researchers managed to heat up a peppercorn-sized sample of two hydrogen isotopes well past the temperature of the Suns core, a process known as inertial confinement fusion (ICF).

ICF is one of two major branches of fusion energy research, with the other being magnetic confinement fusion, a field that has seen its own recent breakthroughs.

During the experiment carried out at the NIF earlier this month, scientists managed to harvest 70 percent of the energy about 1.35 kilojoules worth used by the powerful laser to start the fusion reaction inside the reactor, the BBC reports.

While that may not sound like much, its a big leap in the field. This is a huge advance for fusion and for the entire fusion community, Debbie Callahan, a physicist at the Lawrence Livermore National Laboratory where the NIF is located, told the BBC.

In other words, we are slowly approaching the point where are truly achieving nuclear fusion, or generating a net-positive amount of energy the industrys holy grail that has yet to be reached despite almost a century of research.

The promise is as lucrative as it has ever been: an infinite supply of carbon neutral energy without ever running the risk of a nuclear meltdown.

Scientists at the NIF are particularly excited about their recent experiment as the fusion reaction is starting to be hot enough to lead to more fusion reactions, a process known as ignition.

Self-sustaining burn is essential to getting high yield, Callahan explained to the broadcaster. The burn wave has to propagate into the high density fuel in order to get a lot of fusion energy out.

It was a big moment for the team. Demonstration of ignition has been a major scientific grand challenge since the idea was first published almost 50 years ago, said Jeremy Chittenden, co-director of the Centre for Inertial Fusion Studies at Imperial College London which is helping analyze the data, in a statement. It was the principal reason for the construction of NIF and has been its primary objective for over a decade.

The NIF team have done an extraordinary job, Steven Rose, director of the Center for Inertial Fusion Studies at Imperial, added. This is the most significant advance in inertial fusion since its beginning in 1972.

The research could also have wider reaching implications for the world of physics. The NIF lasers already created the most extreme conditions on Earth, but the new experiment appears to have doubled the previous temperature achieved, said Brian Appelbe, Research Associate in the Centre for Inertial Fusion Studies at Imperial, in the statement. We have entered a regime weve previously never been in this is uncharted territory in our understanding of plasma.

That said, its too early to pop the champagne corks. The team is still going through the data with a fine-tooth comb to ensure that we understand the result, according to Callahan.

The scale of the NIF experiment also leaves something to be desired, despite the high praise. It only yielded about the equivalent to the energy required to boil a kettle, as Chittenden told the BBC.

Its scale may be a long, long way off. But any kind of breakthrough in this field, one thats long vexed some of the worlds greatest working scientists, where the stakes could not be higher, is nothing if not slightly astounding on its own.

READ MORE: US lab stands on threshold of key nuclear fusion goal [BBC]

More on fusion energy: Jeff Bezos Is Helping Build a Fusion Power Plant in the UK

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The Future of Education, According to the World’s Top Thought Leaders and Futurists – FE News

Posted: at 4:13 pm

Further Education News

The FE News Channel gives you the latest education news and updates on emerging education strategies and the#FutureofEducation and the #FutureofWork.

Providing trustworthy and positive Further Education news and views since 2003, we are a digital news channel with a mixture of written word articles, podcasts and videos. Our specialisation is providing you with a mixture of the latest education news, our stance is always positive, sector building and sharing different perspectives and views from thought leaders, to provide you with a think tank of new ideas and solutions to bring the education sector together and come up with new innovative solutions and ideas.

FE News publish exclusive peer to peer thought leadership articles from our feature writers, as well as user generated content across our network of over 3000 Newsrooms, offering multiple sources of the latest education news across the Education and Employability sectors.

FE News also broadcast live events, podcasts with leading experts and thought leaders, webinars, video interviews and Further Education news bulletins so you receive the latest developments inSkills Newsand across the Apprenticeship, Further Education and Employability sectors.

Every week FE News has over 200 articles and new pieces of content per week. We are a news channel providing the latest Further Education News, giving insight from multiple sources on the latest education policy developments, latest strategies, through to our thought leaders who provide blue sky thinking strategy, best practice and innovation to help look into the future developments for education and the future of work.

In Jan 2021, FE News had over 173,000 unique visitors according to Google Analytics and over 200 new pieces of news content every week, from thought leadership articles, to the latest education news via written word, podcasts, video to press releases from across the sector, putting us in the top 2,000 websites in the UK.

We thought it would be helpful to explain how we tier our latest education news content and how you can get involved and understand how you can read the latest daily Further Education news and how we structure our FE Week of content:

Our main features are exclusive and are thought leadership articles and blue sky thinking with experts writing peer to peer news articles about the future of education and the future of work. The focus is solution led thought leadership, sharing best practice, innovation and emerging strategy. These are often articles about the future of education and the future of work, they often then create future education news articles. We limit our main features to a maximum of 20 per week, as they are often about new concepts and new thought processes. Our main features are also exclusive articles responding to the latest education news, maybe an insight from an expert into a policy announcement or response to an education think tank report or a white paper.

FE Voices was originally set up as a section on FE News to give a voice back to the sector. As we now have over 3,000 newsrooms and contributors, FE Voices are usually thought leadership articles, they dont necessarily have to be exclusive, but usually are, they are slightly shorter than Main Features. FE Voices can include more mixed media with the Further Education News articles, such as embedded podcasts and videos. Our sector response articles asking for different comments and opinions to education policy announcements or responding to a report of white paper are usually held in the FE Voices section. If we have a live podcast in an evening or a radio show such as SkillsWorldLive radio show, the next morning we place the FE podcast recording in the FE Voices section.

In sector news we have a blend of content from Press Releases, education resources, reports, education research, white papers from a range of contributors. We have a lot of positive education news articles from colleges, awarding organisations and Apprenticeship Training Providers, press releases from DfE to Think Tanks giving the overview of a report, through to helpful resources to help you with delivering education strategies to your learners and students.

We have a range of education podcasts on FE News, from hour long full production FE podcasts such as SkillsWorldLive in conjunction with the Federation of Awarding Bodies, to weekly podcasts from experts and thought leaders, providing advice and guidance to leaders. FE News also record podcasts at conferences and events, giving you one on one podcasts with education and skills experts on the latest strategies and developments.

We have over 150 education podcasts on FE News, ranging from EdTech podcasts with experts discussing Education 4.0 and how technology is complimenting and transforming education, to podcasts with experts discussing education research, the future of work, how to develop skills systems for jobs of the future to interviews with the Apprenticeship and Skills Minister.

We record our own exclusive FE News podcasts, work in conjunction with sector partners such as FAB to create weekly podcasts and daily education podcasts, through to working with sector leaders creating exclusive education news podcasts.

FE News have over 700 FE Video interviews and have been recording education video interviews with experts for over 12 years. These are usually vox pop video interviews with experts across education and work, discussing blue sky thinking ideas and views about the future of education and work.

FE News has a free events calendar to check out the latest conferences, webinars and events to keep up to date with the latest education news and strategies.

The FE Newsroom is home to your content if you are a FE News contributor. It also help the audience develop relationship with either you as an individual or your organisation as they can click through and box set consume all of your previous thought leadership articles, latest education news press releases, videos and education podcasts.

Do you want to contribute, share your ideas or vision or share a press release?

If you want to write a thought leadership article, share your ideas and vision for the future of education or the future of work, write a press release sharing the latest education news or contribute to a podcast, first of all you need to set up a FE Newsroom login (which is free): once the team have approved your newsroom (all content, newsrooms are all approved by a member of the FE News team- no robots are used in this process!), you can then start adding content (again all articles, videos and podcasts are all approved by the FE News editorial team before they go live on FE News). As all newsrooms and content are approved by the FE News team, there will be a slight delay on the team being able to review and approve content.

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Global Gene Therapy Technologies, Markets & Competitive Landscape Report 2021 with Profiles of 202 Companies and 266 Collaborations in this Area -…

Posted: at 3:55 pm

Dublin, Aug. 20, 2021 (GLOBE NEWSWIRE) -- The "Gene Therapy - Technologies, Markets & Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

Gene therapy technologies are described in detail including viral vectors, nonviral vectors and cell therapy with genetically modified vectors.

Gene therapy is an excellent method of drug delivery and various routes of administration as well as targeted gene therapy are described. There is an introduction to technologies for gene suppression as well as molecular diagnostics to detect and monitor gene expression. Gene editing technologies such as CRISPR-Cas9 and CAR-T cell therapies are also included. Gene therapy can now be combined with antisense techniques such as RNA interference (RNAi), further increasing the therapeutic applications.

Clinical applications of gene therapy are extensive and cover most systems and their disorders. Full chapters are devoted to genetic syndromes, cancer, cardiovascular diseases, neurological disorders and viral infections with emphasis on AIDS. Applications of gene therapy in veterinary medicine, particularly for treating cats and dogs, are included.

Research and development is in progress in both the academic and the industrial sectors. The National Institutes of Health (NIH) of the US is playing an important part. As of 2016, over 2050 clinical trials were completed, were ongoing, or had been approved worldwide. A breakdown of these trials is shown according to the geographical areas and applications.

Since the death of Jesse Gelsinger in the US following a gene therapy treatment, the FDA has further tightened the regulatory control on gene therapy. A further setback was the reports of leukemia following the use of retroviral vectors in successful gene therapy for adenosine deaminase deficiency. Several clinical trials were put on hold and many have resumed now. Four gene medicines have been approved by the FDA. The report also discusses the adverse effects of various vectors, safety regulations and ethical aspects of gene therapy including gene editing and germline gene therapy.

The markets for gene therapy have been difficult to estimate as there only a few approved gene therapy products Gene therapy markets are estimated for the years 2020-2030. The estimates are based on the epidemiology of diseases to be treated with gene therapy, the portion of those who will be eligible for these treatments, competing technologies and the technical developments anticipated in the next decades. In spite of some setbacks, the future for gene therapy is bright. The markets for DNA vaccines are calculated separately as only genetically modified vaccines and those using viral vectors are included in the gene therapy markets

The voluminous literature on gene therapy was reviewed and selected 750 references are appended in the bibliography. The references are constantly updated. The text is supplemented with 79 tables and 25 figures.

Profiles of 202 companies involved in developing gene therapy are presented along with 266 collaborations. There were only 44 companies involved in this area in 1995. In spite of some failures and mergers, the number of companies has increased more than 4-fold in 2 decades. These companies have been followed up since they were the topic of a book on gene therapy companies by the author of this report.

Benefits of this report

Story continues

Up-to-date on-stop information on gene therapy with 79 tables and 25 figures

Evaluation of gene therapy technologies

750 selected references from the literature

Estimates of gene therapy markets from 2020-2030

Profiles of 202 companies involved and collaborations in this area

Who should read this report?

Biotechnology companies developing gene therapy

Academic institutions doing research in gene therapy

Drug delivery companies

Pharmaceutical companies interested in gene therapy

Gene therapy companies

Venture capital and investment companies

Key Topics Covered:

Executive Summary

1. Introduction

2. Gene Therapy Technologies

3. Clinical Applications of Gene Therapy

4. Gene Therapy of Genetic Disorders

5. Gene Therapy of Cancer

6. Gene Therapy of Neurological Disorders

7. Gene Therapy of Cardiovascular Disorders

8. Gene therapy of viral infections

9. Research, Development and Future of Gene Therapy

10. Regulatory, Safety, Ethical Patent Issues of Gene Therapy

11. Markets for Gene Therapy

12. Companies involved in Gene Therapy

13. References

For more information about this report visit https://www.researchandmarkets.com/r/v69ou

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Regenerative medicine nears banner year with $14.1B cash infusion, regulatory milestones and a well-stocked pipeline – FierceBiotech

Posted: at 3:55 pm

For a long time, gene and cell therapies were a treatment option for the future. Now, the pace of development is moving at breakneck speed, with a number of firsts and $14.1billion in financing collected over the initial half of the year.

The Alliance for Regenerative Medicine has documented the acceleration on all fronts in a new report looking at the first half of 2021.

Most notably was Intellias demonstration of CRISPR gene-editing in humans through phase 1 data for patients with transthyretin (ATTR) amyloidosis. But thats not all for regenerative medicine, which includes cell and gene therapies, gene editing and tissue-based therapies.

Companies developing these therapies have collected $14.1 billion in the first half alone, which is 71% of what was raised during all of 2020. The alliance called this surge the strongest half on record. 2020 already broke financing records, with $20 billion, and the report suggests 2021 could exceed that total.

RELATED:Intellia hits a 'home run' with gene-editing results, setting up entire field for a grand slam

Cell-based immuno-oncology has for the first time surpassed gene therapy in financing, notching $6.6 billion compared to $6.4 billion, respectively. The broader category of cell therapy, including stem cell treatments for Parkinson's disease, meanwhilepicked up $1.1 billion.

Gene therapies and gene-modified cell therapy products are on track to notch the highest annual number of regulatory approvals. Three have already been approved. Bluebird bios Skysona nabbed an EU nod for the rare neuromuscular disease cerebral adrenoleukodystrophy. Bristol Myers Squibb and bluebirds multiple myeloma CAR-T drug Abecma was cleared by the FDA in late March. And Bristol Myers long-awaited CAR-T liso-cel, now called Breyanzi, was approved in February.

Waiting in the regulatory queue in the U.S. and EU isJohnson & Johnson and Legend Bios cilta-cel in multiple myeloma, which will compete with Abecma. Other companies have approvals pending around the world.

Even with these approvals, however, cell and gene therapies face hurdles once they are cleared for the market. Bluebird bio, for instance, has pulled back from European markets after failing to reach a consensus on pricing for the one-time treatment Zynteglo.

RELATED: With the pricing situation 'untenable' in Europe, bluebird will wind down its operations in the 'broken' market

The pipeline is nevertheless filled to the brim with new therapies. The report counted 1,320 industry-sponsored trials underway worldwide, including 158 that are in phase 3. Academic and other research is responsible for an additional 1,328 non-industry trialsincluding 85 late-stage studies.

Indications run the gamut of diseases, but are mostly concentrated in oncology for the industry-sponsored trials, followed by central nervous system (CNS) disorders and rare genetic diseases. Academic research similarly focuses on oncology, followed by infectious diseases and CNS.

CAR-T therapies, which take a patients own cells and power them up to fight cancer before being returned to the body, have been particularly dominate in R&D. Abecma is one example, but the J&J-Legend cilta-cel showed some promising data in June, with a 98% overall response rate in multiple myeloma. The therapy is currently being reviewed by EU and U.S. regulators, with a decision expected later this year.

RELATED:ASCO: J&J's anti-BCMA CAR-T pads its case ahead of speedy review and Bristol Myers showdown

More readouts are expected from Precision BioSciences and CRISPR Therapeutics, which are working on separate BCMA-targeted CAR-T therapies.

The alliance counts 566 companies as developing regenerative medicines and advanced therapies in the U.S. and 588 industry-sponsored trials with U.S. sites.

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This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous – The New York Times

Posted: at 3:55 pm

Heidi Marsh, 46, of Seattle, tested positive for the PALB2 mutation after her mother a breast cancer and pancreatic cancer patient was found to have it. She said her own doctor was unaware of the gene.

My OB-GYN was aware of my moms history and never suggested genetic testing, Ms. Marsh said. She never heard of it. I educated her. The oncologist she sent me to did not suggest surgery.

But Seattle Cancer Care Alliance, a partner of Fred Hutchinson Cancer Research Center, where Ms. Marshs mother had been an oncology nurse, did know about the gene mutation. The group immediately put together a team that included a surgical oncologist, a pancreatic cancer specialist, a geneticist, a nutritionist and a social worker.

This has been life-changing, said Ms. Marsh, who had her fallopian tubes removed in April. (She was told most ovarian cancer first occurs in the tubes. She plans to remove her ovaries after menopause.)

She will have breast monitoring with alternating mammograms and breast M.R.I.s every six months. She has already had an endoscopic ultrasound to look at her pancreas.

She has found a Facebook group, PALB2 Warriors, to be helpful. Because she has a background in health care she was a phlebotomist she says she looks further than individual postings, to studies that are placebo-controlled and peer-reviewed for information. But when it comes to personal stories of experience with prophylactic mastectomies and reconstruction, she says that is invaluable.

This was not remotely on my radar screen, she said. In one sense I feel empowered. But I also feel like I am waiting for the other shoe to drop, that cancer will be inevitable.

But mostly, she is thankful that she knows about PALB2 and the risks involved.

Its an alarm clock and a wake-up call, she said. You can do something about it if you choose.

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FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug – UT Southwestern

Posted: at 3:55 pm

DALLAS Aug. 21, 2021 A first-in-kind kidney cancer drug developed from laboratory and translational studies conducted at UTSouthwestern Medical Center received approval from the Food and Drug Administration, providing a new treatment for patients with familial kidney cancer.

FDA approval of belzutifan culminates a 25-year journey at UTSW from gene discovery to a first-in-class drug.

Mercks belzutifan grew out of the discovery at UTSouthwestern of a protein, HIF-2, that is key to fuel the growth of kidney and other cancers. HIF-2 was discovered by Steven McKnight, Ph.D., Professor of Biochemistry.

This is an exciting milestone for patients with inherited forms of kidney cancer who are in need of more effective therapies, said David Russell, Ph.D., Vice Provost and Dean of Research, and Professor of Molecular Genetics, who collaborated in the early stages of the research.

The drug, once called PT2977, was developed based on a backbone discovered by UTSW researchers, with further drug development efforts conducted by a spinoff company named Peloton Therapeutics, which was launched on the UTSW campus and eventually acquired by Merck.

Drs. McKnight and Russell first identified HIF-2 in the 1990s.

HIF-2 was considered undruggable for many years until two more UTSW scientists at the time Richard Bruick, Ph.D., Professor of Biochemistry, and Kevin Gardner, Ph.D., Professor of Biophysics, who also directs a structural biology center at the City University of New York did the structural and biochemical work showing that the HIF-2 molecule contains a pocket that is potentially druggable. The two scientists then identified multiple compounds that fit into this pocket and inhibited the activity of HIF-2.

The history of belzutifans development demonstrates the value of cross-disciplinary collaborations at academic medical centers and how that can translate to new treatments for diseases, said Dr. Russell. It also underscores the value of investing in basic science discoveries at the core of advancements in medicine.

In 2011, several researchers spun off Peloton Therapeutics, and by 2019, when Merck acquired the company, at least three HIF-2 agents were under investigation.

James Brugarolas, M.D., Ph.D., Director of the UTSW Kidney Cancer Program

James Brugarolas, M.D., Ph.D., Director of the Kidney Cancer Program at UTSouthwesterns Harold C. Simmons Comprehensive Cancer Center, showed that the drug was effective against kidney cancer.

With funding from a prestigious National Cancer Institute SPORE award, they showed in a publication inNaturein 2016 that the drug was able to inhibit HIF-2in human kidney tumors transplanted into mice and stop their growth.

This and other studies led to the first clinical trial of PT2385, a precursor to PT2977, which became belzutifan. The trial, which was led by the UTSW Kidney Cancer Program, showed that the drug was well-tolerated and active.

The approval of belzutifan represents a new paradigm in the treatment of kidney cancer, said Dr. Brugarolas, Professor of Internal Medicine. By exclusively targeting HIF-2, which is essential for kidney cancers but dispensable for normal processes, belzutifan specifically disables cancer cells while sparing normal cells. Belzutifan is the best-tolerated kidney cancer drug today and one suitable for patients with familial kidney cancer. It is a testament to the prowess of designer drugs and carefully chosen targets of which it is a prime example.

1997UTSouthwestern biochemist Steven McKnight, Ph.D., and molecular geneticist David Russell, Ph.D., report the discovery of the HIF-2 gene, which they call EPAS1. The team shows that HIF-2 binds to another protein, HIF-1. The HIF-2 partner functions like a pair of tweezers to grab DNA. HIF-2 binds DNA at specific places to initiate the production of other proteins such as VEGF, which support kidney cancer growth.

2003The laboratories of Richard Bruick, Ph.D., and Kevin Gardner, Ph.D., uncover aspects of the atomic blueprint of HIF-2. They show how HIF-2 docks with HIF-1 to assemble into a functional HIF-2 complex. They identify a cavity within the HIF-2 protein, hypothesizing that it may offer a foothold for a drug. Working with UTSouthwesterns High-Throughput Screening laboratory, Drs. Bruick and Gardner develop a test to identify chemicals among 200,000 drug-like molecules that bind to the HIF-2 cavity, preventing HIF-2 binding to HIF-1. By interfering with HIF-2 binding to HIF-1, these compounds block HIF-2 action. The most promising chemicals undergo a refinement process by medicinal chemists at UTSouthwestern.

2010Peloton Therapeutics is founded by UTSW researchers to develop the HIF-2 blocking chemicals into drugs. Peloton scientists create libraries of related compounds, ultimately identifying PT2385 and PT2977 to test in humans. A related drug, PT2399, is identified for laboratory work.

2016Dr. James Brugarolas validates HIF-2 as a target in kidney cancer. In experiments incorporating more than 250 mice transplanted with human kidney tumors, researchers show that PT2399 blocks HIF-2 while not affecting related proteins, is active against 50% of human kidney tumors, and has more activity and is better tolerated than sunitinib (the most commonly used drug for renal cancer treatment at the time).

2018Dr. Kevin Courtney reports the results of a phase 1 clinical trial testing PT2385 in humans. The trial represents the first-in-human study of a first-in-class inhibitor of HIF-2. The trial, which involves 51 patients, shows that PT2385 is safe, well tolerated, and active against ccRCC in humans. More than 50 percent of patients see their cancer regress or stabilize. A patient of Dr. Brugarolas sees benefit for more than a year despite prior progression on seven drugs.

2019U.S. drug manufacturer Merck acquires Peloton Therapeutics for $1.05 billion, with an additional $1.15 billion contingent on sales and regulatory milestones.

2020Through studies of tumor biopsy samples from patients who participated in the Phase 1 clinical trial, Drs. Courtney, Brugarolas, and Ivan Pedrosa, M.D., Ph.D., report the identification of drug resistance mutations in patients, establishing HIF-2 as the first-known core dependency of kidney cancer.

Dr. Brugarolas holds The Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. McKnight holds the Distinguished Chair in Basic Biomedical Research. Dr. Pedrosa holds the Jack Reynolds, M.D., Chair in Radiology. Dr. Russell holds the Eugene McDermott Distinguished Chair in Molecular Genetics. Disclosures: UTSouthwestern and some of its researchers will receive financial compensation, through prior agreements with Peloton, based on belzutifans FDA approval.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty has received six Nobel Prizes, and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in about 80 specialties to more than 117,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits a year.

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FDA approval of belzutifan culminates 25-year journey at UTSW from gene discovery to a first-in-class drug - UT Southwestern

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