Every year, without fail, the Endpoints 11 proves to be the most challenging project I face — and definitely remains the most fun.
In an industry where ambition and zeal are trademarks of the most exciting biotechs, how do you narrow the list down to 11 of the most worthy new drug developers to hit the scene?
Without doubt the science remains the crucial element. You have to look for an important advance to make your mark in biotech, and that means tracking down cutting-edge labs that have become skilled at exploring new opportunities. Drug development is extraordinarily expensive, and that means the backers have to offer credibility with a rep for playing out the game. You can’t have a syndicate of shaky players when you embark on a journey of years. And then there’s the management team: the people betting a big chunk of their lives that they can accomplish something of real importance.
By definition, this is a group that still has a lot to prove, and a series of missteps will take you right off the tracks. So that takes you back to the management team, and the quality of the people they can recruit into the company. Staying focused, identifying the small steps that lead to the big finale, is not an easy task.
Up until now, the Endpoints 11 has been a solo endeavor. But that’s all over. Ryan Cross, Andrew Dunn and Kyle LaHucik stepped in to write the bulk of the report this year. Their contributions go deep here and I couldn’t be happier in seeing the team come together as we’ve grown the publication. Kudos also to executive editor Drew Armstrong, who so ably led the team and offered plenty of suggestions for improvements.
No doubt more will be coming in the years ahead.
In the meantime, I hope you enjoy our list and take away some lessons on who and what gets noticed in a tougher industry environment. Everyone’s bar for success and survival has been raised several notches. That makes the Endpoints 11 more important than ever as we offer a shoutout to some of the standouts. And if you nominated a company you don’t see here, remember that planning for next year’s event is already underway.
- Aera Therapeutics
- Chroma Medicine
- Enveda Biosciences
- Immuneel Therapeutics
- Isomorphic Labs
- Maze Therapeutics
- Orbital Therapeutics
- ReNAgade Therapeutics
- Seismic Therapeutic
- Ultima Genomics
Aera Therapeutics: Feng Zhang bets on solving gene therapy’s biggest problem: ‘Delivery is such a big bottleneck’
- CEO Akin Akinc
- Total raised $193M
- Headquarters Cambridge, MA
Backers: ARCH Venture Partners, GV and Lux Capital
The scoop: Feng Zhang says he doesn’t think of himself as a serial entrepreneur, although his track record is starting to say otherwise. By the summer of 2021, just a decade after he began developing the DNA-altering tool known as CRISPR, he’d co-founded six biotech companies and was itching to launch his seventh.
His latest laboratory creation was a newfangled way to deliver genes into cells with nanoparticles made from mysterious, under-studied virus-like proteins hiding in the human genome. The work was going to press in Science that August, and he knew it would make a splash, so he began calling investors to gauge their interest.
“There aren’t too many scientists on the planet like Feng,” said David Schenkein, a co-leader of the life science investment team at GV — Alphabet’s investment arm. “When you get a phone call from him asking if you want to go out for dinner to hear about a new technology, the answer’s yes.”
Zhang made his pitch to Schenkein and GV partners Krishna Yeshwant and Issi Rozen over an Italian meal outside the Liberty Hotel in Boston. It was no secret to the table that CRISPR was facing a delivery dilemma. Most gene editing companies were focused on editing cells in the blood, eye, or liver — the easiest places to reach with existing delivery technologies, but just a sliver of the places where CRISPR might prove curative.
The group agreed that the creation of new tools to edit or replace genes was outpacing the ideas for getting those therapies into the right parts of the body.
“We’re limited by delivery,” Zhang said in an interview with Endpoints News. “And we really need to open up this floodgate so that we can treat more diseases.”
Zhang’s paper showed that the nanoparticles could slip CRISPR into cells in a dish. Since the nanoparticles were made from proteins that came from the human body, they might evade the immune reactions that hamper other delivery vessels. Unpublished work suggested that the nanoparticles could be manufactured far more easily than the traditional viral vectors deployed in gene therapy and that they could be engineered to target specific cell types.
It would be a long road to proving that the technology worked in people, or that it could meaningfully expand the list of organs that genetic medicines can reach. But the investors were wooed by the possibilities.
“It was like check, check, check,” down GV’s wish list for a new delivery technology, Schenkein said. “It was pretty clear to us that this could be the breakthrough we were looking for.”
The resulting startup, Aera Therapeutics, emerged from stealth earlier this year with $193 million from ARCH Venture Partners, GV, and Lux Capital. To lead the startup, Zhang helped recruit Akin Akinc, a longtime Alnylam scientist who helmed the development of the lipid nanoparticles used in the first gene-silencing RNAi therapy.
“When you get a message from Feng, you take it,” Akinc said. He was intrigued that Aera was pursuing “something different” and was sold by its heavy-hitting board, including ARCH managing director Bob Nelsen and his old boss, former Alnylam CEO John Maraganore.
Zhang’s initial nanoparticle was built from a human protein called PEG10, but there could be upwards of 80 similar proteins that form virus-like structures in the human body, Akinc said. Aera is focused on figuring out how and if those other proteins might deliver genetic cargo.
“This is a hard problem, and it’s going to take time,” Akinc said.
He hopes that Aera will have therapies in clinical trials within five years. And although he thinks it’s still too early to think about specific diseases or targets, he emphasized that Aera does not want to copy the all-too-similar pipelines of other genetic medicine companies.
“We’re not going to be that interested in finding yet another way to deliver to hepatocytes in the liver. We want to look for things where we can have a big impact,” Akinc said.
That could include targeting organs, including the heart, lung, kidney, and central nervous system, he added, as well as developing in vivo therapies for conditions that currently require removing blood or immune cells from the body.
Aera also licensed a couple kinds of DNA-altering enzymes from Zhang’s lab that are roughly one-third the size of the original CRISPR editors, which could make them easier to stuff into the protein nanoparticles. Zhang remains an active advisor to the company, which he thinks will speed up the development of his protein nanoparticles far faster than he could do alone.
“Because delivery is such a big bottleneck for the entire gene therapy field, we need to be very serious about it if we want to make a dent,” Zhang said. — Ryan Cross
ArsenalBio: Getting to the holy grail in oncology R&D is going to take some bold experimentation
- CEO Ken Drazan
- CMO Susie Jun
- Total raised $405.81M
- Headquarters South San Francisco, CA
Backers: New investors in the $220 million B round last fall included SoftBank Vision Fund 2, Bristol Myers Squibb, Byers Capital, Emerson Collective Investments, Green Sands, Hitachi Ventures, Sixth Street with a group of founding investors involving Parker Institute for Cancer Immunotherapy, Westlake Village BioPartners, the University of California, San Francisco Foundation Investment Company, Euclidean Capital, Waycross Ventures, and Kleiner Perkins.
The scoop: If you want to examine an ambitious scientific mission in pursuit of the holy grail of oncology R&D, it doesn’t get much better than ArsenalBio.
When the first two big pioneers in CAR-T came along at Novartis and Kite, they were able to prove that engineering patients’ T cells to go after blood cancers could create transformational therapies. By the time the approvals came along, the focus in the lab had already jumped to solid tumors, and next-gen companies would take aim at off-the-shelf allogeneic therapies that wouldn’t delay treatment.
It has proved to be an incredibly difficult journey.
Hematological tumors are relatively easy. You get the T cells to the target, they kill tumor cells. Solid tumors are a completely different story — just getting T cells to the tumor isn’t enough. Their defenses have raised issues with cell exhaustion, targets that overlap with normal tissues — raising problems with off-target toxicity. And when you’re working with patients’ cells, you need to find a way that allows for quick, reliable manufacturing.
“So what we’re trying to do is address all of those problems at the same time,” Arsenal CMO Susie Jun says.
That starts by keeping things as simple as possible.
With enough problems already on their autologous plate, they’re initially foregoing the allogeneic approach for personalized therapy, so they can take cell rejection off the table and focus on the rest of the obstacles. They’re sticking with CAR-T to avoid the diversity issues associated with TCRs or TILs.
The complex challenge that remains has been tackled with machine-learning tech — part of the biotech’s reliance on tapping experts in different fields — to come up with a standard set of solutions to the problems they face.
They use CRISPR to insert a “very large” piece of DNA that gives them “a hard drive of sorts” — adding a series of functional, DNA-based modules that are put into the DNA template that should perform uniformly in cells with trackable results, Jun says.
That in itself — identifying and making the most efficient chop, inserting a big piece of DNA — was an advance they had to work out on their own, she adds, the first challenge in the gamut of challenges to come.
One of those modules they insert is a logic gate for twin targets co-expressed in the tumor alone. Another module encodes short hairpin RNAs, down-regulating expression of RNA in the T cells, modulating T cell functions and adding to the repertoire in overcoming the tumor’s defenses. And the modules have to work concurrently as planned.
Their screening approach gives researchers the chance to review thousands of drug constructs before they put it to the preclinical test, which is now making the leap into the clinic and the supreme test in humans.
Phase I is going to take time, Jun says. It’s a standard dose escalation study, but that’s not quick or easy when you’re using something this complex.
With well over 200 staffers now and major league investors, multidisciplinary research teams have to stay on track. And that’s no easy task either.
Success is based on teams, measured by quarters of the year.
“In order to get there we’re going to have to make a series of scientific advances, things that no one has ever done before,” Jun says.
“We didn’t tell them it was impossible,” she says about her research group. “We just told them, ‘Would you be able to come up with something where you could iterate thousands of combinations?’ We give them one-quarter milestones. Can you do this in a quarter? And each quarter they come up with better solutions as we come along and our speed of iteration has come along as well.
“It really is the vision. We have collected a lot of scientific experts across many disciplines. We have synthetic biologists, computation biologists, automation specialists, immunologists, we have cell biologists, we have a bunch of different scientific disciplines that don’t typically work together and don’t typically work in the field of drug development. So we set a vision that we want to cure solid tumors, which is a big, big vision.”
The biotech got started with launch money in a 2019 Series A round of $85 million from the Parker Institute of Cancer Immunotherapy, their close colleagues at Westlake, UCSF and others. Then Arsenal added a $220 million Series B to power forward with contributions from the likes of Bristol Myers Squibb — also a research partner — and SoftBank Vision Fund 2. Add in a research alliance with Genentech and a highly experienced team in pursuit of solid tumors, and you have a leading effort in the field.
To be sure, lots of money, great science and deep-pocket partners are all great to have. But we’ve seen some of this funding team watch Tmunity and Tessa go down in flames after touting grand visions in cell therapy, and success is not guaranteed. But win or lose, it will be fascinating to watch. — John Carroll
Chroma Medicine: Betting the next frontier of genomic medicine doesn’t touch genes
- CEO Catherine Stehman-Breen
- CSO Vic Myer
- Total raised $257M
- Headquarters Boston
Backers: Chroma’s $135 million Series B announced in March was led by GV, with new investors including ARCH Venture Partners, DCVC Bio, Mubadala Capital, and Sixth Street. Atlas Venture and Newpath Partners were the first backers behind its 2020 founding, with Cormorant Asset Management leading its Series A.
The scoop: A technology that doesn’t even edit genes may be at the heart of the next great gene editing race.
Chroma Medicine has emerged as a leader in epigenetic editing, an approach that changes gene expression instead of modifying DNA itself. The Boston-based biotech’s approach adds or removes methyl groups, the simple molecules that attach to DNA and turn genes on or off. CEO Catherine Stehman-Breen said the approach should bring durable changes to gene expression from a single treatment.
“Applying or removing these methyl marks changes the conformation of the DNA,” Stehman-Breen said. “If you apply the methyl marks, it closes down that DNA and silences gene expression. If you remove those methyl marks, it makes those genes available and accessible for gene expression.”
Chroma’s story begins about a decade ago, when CRISPR pioneer Jennifer Doudna stopped by the office of Jonathan Weissman, then a biologist at the University of California, San Francisco. Doudna had recently published her landmark 2012 paper on CRISPR-Cas9, and the two wondered what else they could do with this new editing system.
Tinkering with the CRISPR system led to work described in a 2013 paper that modified gene expression instead of genes. That approach was a “great discovery tool,” Weissman said, helping find genes worth targeting with CRISPR, but falling short of being a drug itself. Once the Cas9 enzyme went away, gene expression returned.
Further research by Weissman and UCSF’s Luke Gilbert showed that methylating DNA could permanently silence genes. Weissman called it a “hit-and-run” approach that uses CRISPR’s permanence without worrying about breaking and fixing DNA strands.
Chroma sought to move the “hit and run” work forward, adding on gene editing pioneers David Liu and Keith Joung as scientific co-founders. In 2021, Chroma bought the Milan-based epigenetic startup called Epsilen Bio, counting genomic researchers Luigi Naldini and Angelo Lombardo as co-founders as well.
Even as other biotechs are advancing next-gen editing approaches like base and prime editing, Chroma’s founders are confident epigenetic editing will carve its own space.
Some genetic diseases, like cystic fibrosis, need a change to the DNA sequence and are best served by DNA-cutting approaches. But many stem from a toxic protein, where “epigenetic silencing is really the more elegant, more perfect solution,” Weissman said.
“You could make a double-stranded break with all the risks of the reaction, or use prime or base editing to somehow damage the gene encoding for the toxic protein, but at the end of the day it’s a harder reaction,” Weissman said. “And you are left with a crippled message that is probably going to be subject to nonsense-mediated decay and a crippled protein that may no longer be toxic, but is still going to be expressed for the rest of the life of the patient.”
So far, Chroma has presented a handful of research findings in cells and in mice. Its epigenetic editor silenced PCSK9, a gene linked to cholesterol, in mice by more than 99%.
While there are multiple FDA-approved drugs targeting PCSK9, Stehman-Breen said she believes Chroma’s program “has legs from a commercial standpoint” by pursuing better efficacy. Chroma has now started non-human primate studies.
Chroma is also working on hepatitis B, a disease where epigenetic editing could stand apart from the editing field. Chroma can target both the circular-shaped DNA of the hepatitis B virus and the bits of viral DNA integrated into human cells. Typical editors like CRISPR-Cas9 would cut the viral DNA’s circular shape, possibly straightening out that DNA, leaving it liable to integrate into a cell’s DNA.
Despite the excitement, there’s a long road ahead. Stehman-Breen declined to provide a timeline for a first therapy entering the clinic, beyond saying the company is focused on getting there as soon as possible. Both the PCSK9 and hepatitis B programs are running in parallel, with Chroma expecting they could start human testing around the same time.
And there’s no lack of competition. North Carolina-based Tune Therapeutics has already presented non-human primate data with a PCSK9 epigenetic editor, while Epic Bio, a San Francisco-based epigenetic-focused startup, plans to file its first IND some time this year.
“We keep an eye on what our competitors are doing,” Stehman-Breen said, “but we feel passionately we have the right secret sauce to be able to do something really special for patients.” — Andrew Dunn
Enveda Biosciences: Getting back to nature to map plant chemistry
- CEO Viswa Colluru
- CSO Sotirios Karathanasis
- Total raised $175M
- Headquarters Boulder, CO
Backers: Lux Capital led the company’s Series A, and Lux offshoots at the new VC firm Dimension led the Series B. Additional backers include Swedish investor Kinnevik, KKR co-chair Henry Kravis, FPV, True Ventures, Wireframe, Two Sigma Ventures, Hummingbird VC, Catalio Capital, Lifeforce Capital and Recursion CEO Chris Gibson, among others.
The scoop: As a child growing up in India, Viswa Colluru quickly bounced back from a battle with jaundice, returning to school in a matter of days, thanks to medicinal plants.
After entering drug development as an adult, he came to view such remedies as nothing more than a placebo. That was until his wedding in 2018, when his father happened to remind him of the power of nature and its long history in easing ailments.
Intrigued, Colluru found there was promising science to back up his father’s position. He created Enveda Biosciences, a four-year-old startup that’s mapping the chemistry of plants to create new therapeutics. Its first big test will come next year, when the biotech plans to begin at least two clinical trials of oral medicines.
“I found myself as having maybe the perfect amount of experience and naïveté, upbringing and exposure, to be able to champion this idea,” Colluru told Endpoints.
If he hadn’t used traditional medicine as a kid in India, including ginger for nausea and a plant for jaundice, he might not have had the conviction. He dug through the pharmaceutical industry’s relationship with natural products and drugs derived from plants. Morphine has poppy seed to thank. Aspirin, the anti-diabetic metformin, the blood thinner warfarin and others have all come from nature.
“It’s funny, when you think about the core of Enveda being natural products, every pharma company would scoff at that and be like, ‘Look, we tried that. It’s not an interesting place,’” said Shaquille Vayda, principal at Lux Capital, an early investor in Enveda.
Colluru didn’t form Enveda based on the next big gene editing tool or eye-popping enzyme like other flashy biotechs that emerged from academic labs during the biotech boom. Rather, he turned to the well-worn path of small-molecule drugs, with a twist. Enveda’s scientists are finding new bioactive molecules, using mass spectrometry and machine learning, while the company’s search engine stores all the data. Enveda Search, as it’s aptly called, comprises new molecules in nature, along with annotations on the molecules’ properties, structure and activity.
In contrast, drug development typically starts with identifying druggable proteins and then targeting them with synthetic molecules.
Founded in 2019, the startup had originally sought to go after Wilson disease, NASH and Parkinson’s, but pivoted to inflammation and immunology. Enveda’s pipeline is made up of 10 programs.
The lead asset is an NLRP3 inflammasome inhibitor, and plans call for the pill to enter human studies next year in inflammatory bowel disease. Novo Nordisk, Novartis, Roche and others have tapped into the target in recent years.
Enveda’s second program, a neutrophil-modulating oral drug, will first be investigated in atopic dermatitis, a disease that causes inflammation, redness, and irritation of the skin in 25 million US patients. The company is entering a crowded field with Sanofi and Regeneron’s megablockbuster Dupixent, Eli Lilly’s lebrikizumab (under FDA review) and a group of biotechs trying to catch up, like Dermavant and Apogee Therapeutics.
Other companies targeting these diseases don’t have the same back-to-nature approach. But Enveda isn’t alone in wider drug development. Montai Health raised $50 million to chart anthromolecule chemistry — molecules that have evolved alongside humans that could treat chronic diseases. Brightseed is attempting to turn to the natural world for medicines, supplements and food ingredients.
Enveda was born four years ago, when Collura left his product manager role at Recursion Pharmaceuticals. He pumped $50,000 of his own money into the project and collected another $220,000 from friends and family.
Chris Gibson, Recursion’s CEO and an early investor in Enveda, said Colluru’s company is “at the top of the list” of other techbio startups that he’s “super-jazzed about.”
“You can see the fingerprints of Recursion all across that company and that’s an awesome feeling because it means our mission, our impact is broader than just what we’re doing here at Recursion,” Gibson said.
Around the middle of 2024, Colluru said Enveda should have their pitch ready for the next round of financing. The startup disclosed a $51 million extension to its Series B in April. Enveda currently predicts it has the cash to get into the middle or third quarter of 2025.
To stretch the money, Colluru set up shop in Boulder, CO, and Hyderabad, India.
Therapeutics are just the beginning for Enveda. Animal health, diagnostics, manufacturing, agrochemicals — they could all benefit from new insights into plant and human chemistry, Colluru said.
“The potential here is massive, but there’s enough wood to chop just on the therapeutics side, where I think there’s a $50 billion company to be built just on therapeutics alone in the next decade,” said Zavain Dar, a co-founder of VC firm Dimension, Enveda’s Series B lead investor. — Kyle LaHucik
Immuneel Therapeutics: An unheralded biotech trying to bring a $50,000 CAR-T to India — and the world
- COO Arun Anand
- Total raised $26M
- Headquarters Bengaluru, India
Backers: The biotech raised a $15 million Series A in 2022, and VC backers include F-Prime Capital, Eight Road Ventures, and Khosla Ventures.
The scoop: Some of the most provocative cell therapy work is happening halfway around the globe from Kendall Square, on the eighth floor of a hospital in Bengaluru, India.
The Indian biotech Immuneel Therapeutics is on the verge of a grand commercial challenge to the drug industry, aiming to bring cell and gene therapies to the rest of the world at a fraction of current prices.
Immuneel has moved quickly, starting as an idea volleyed over breakfast in New York in late 2018 among its three founders: Kiran Mazumdar-Shaw, the billionaire founder of the Indian drugmaking giant Biocon, the Pulitzer Prize-winning oncologist and author Siddhartha Mukherjee, and 5AM Ventures’ Kush Parmar.
The trio carries personal ties to India and wanted to put the young country of 1.4 billion people on the CAR-T map. Immuneel has now grown to a 100-employee startup that has applied for what could be the first cell therapy approved in India to treat leukemias and lymphomas.
In the US, CAR-T therapies cost $375,000 and up. Arun Anand, the company’s chief operating officer, said he expects, pending the regulators’ OK, a starting price at one-third to one-fourth of US pricing. The goal is to drop to one-tenth of US prices in three to five years, meaning selling a CAR-T therapy in India for $50,000 or less.
Those price drops are possible from running a lean operation in India, where every dollar goes further, Anand said, adding they have the right mix of talent, strategy, and focus.
“We knew there was no way any Indian patient could pay the kind of price that CAR-Ts were demanding in the Western world,” Mazumdar-Shaw said. “We are not pursuing a model that wants a 95% operating margin. We are happy with a much lower, but sustainable, margin.”
It’s not often that a startup biotech puts an emphasis on commercial innovation and making drugs affordable to the developing world.
“Access and innovation are inextricably linked. They are not opposed to another,” Mukherjee said. “Innovation doesn’t necessarily mean making a new biological reagent. It might mean solving an engineering problem. It might mean running a new kind of trial. It might mean solving supply-chain issues.”
That lean focus is also reflected in its unconventional headquarters: the eighth floor of a hospital in Bengaluru, directly above the bone-marrow transplant ward where its cell therapies could be used.
“We buried ourselves inside so we would have constant minute-to-minute, hour-to-hour communications with the treating physicians,” Mukherjee said. “That model turned out to be an incredible provocation and an incredible way to think about things, because this is not a drug, it’s a living drug.”
Challenges have been plentiful in getting up and running. “The standard pharmaceutical partners wouldn’t touch us,” Mukherjee said, so the company eventually licensed a CAR-T program with solid clinical results from a hospital in Barcelona. Immuneel has now run its own India-based trial with that CAR-T program and applied for Indian regulatory approval.
Immuneel will also face the challenge of grappling with India’s historically shaky reputation in drug manufacturing. Reports over the years have highlighted safety problems and lax oversight in making cheap generic drugs. Immuneel hopes to cheaply produce cell therapies, which carry another magnitude of complexity compared to pills or monoclonal antibodies.
As the team planned to build its hospital-based lab, Covid-19 hit. Despite lockdowns, Immuneel built its lab in about six months. Early on, Anand talked with the construction crew to let them know what they were building. Contractors who normally travel back home on weekends stayed in a bubble for months, about a quarter-mile from the hospital, working around the clock, often until midnight during the pandemic.
“It’s one thing speaking of a mission in a lofty, ideal statement,” Anand said, “but another in taking people to a hospital and showing them what it would be to have a child who is 3 or 4 with leukemia and struggling.”
Immuneel has now completed the first Phase II CAR-T study in India, presenting data last December showing a 77% overall response rate in late-stage leukemia and lymphoma patients. “This is world-class data,” Mukherjee said.
Competition appears to be limited for Immuneel, although an India-based biotech called ImmunoACT has also been working on bringing CAR-T therapy to India. ImmunoACT has also said it hopes to slash prices, and appears to be targeting an approval in 2024 for its most advanced program.
As Immuneel waits for Indian regulators on what could be the country’s first CAR-T therapy, its leaders are also looking ahead. The company is developing its own pipeline of cell and gene therapies, likely to divulge more details over the next year or so. And Immuneel hopes to bring this model to more low- and middle-income countries that would otherwise have no access to these advanced therapies.
“If we can do it in India and if we can deliver it at the price point that we want to, we can take it anywhere in the world,” Mazumdar-Shaw said. — Andrew Dunn
Isomorphic Labs: Demis Hassabis sees a ‘sweet spot’ for an AI revolution in biotech
- CEO Demis Hassabis
- CSO Miles Congreve
- Total raised Undisclosed
- Headquarters London
Backers: Isomorphic is an Alphabet company, effectively spun out of the tech giant’s AI research unit called DeepMind. It declined to disclose how much funding it has received.
The scoop: For all the hype surrounding AI, the field’s clearest success has likely been AlphaFold2, an AI system that accurately predicts protein structures.
In 2020, AlphaFold2 dominated a protein-folding competition, leading experts to declare the longstanding scientific challenge effectively solved. Since being openly released in 2021, over a million researchers have used AlphaFold, its inventors won some of science’s most prestigious awards, and it’s fueled a crop of biotech startups striving to do “AlphaFold-for-X.”
Yet Demis Hassabis sees AlphaFold as only the beginning. Hassabis is best known for leading the AI ambitions of the tech giant Alphabet as CEO of Google DeepMind. But the 47-year-old is also the CEO of Isomorphic Labs, a new secretive Alphabet-backed company that thinks AI can do far more than predict the shape of proteins. Hassabis believes AI will upend the whole drug discovery process.
“AlphaFold was the proof point to do Isomorphic,” Hassabis told Endpoints in the first interview he’s given about Isomorphic, which publicly launched in November 2021.
Hassabis, who studied computer science at Cambridge University and later earned a PhD in cognitive neuroscience at University College London, said he mulled the idea of focusing AI on drug discovery for a “very long time.” AlphaFold’s success instilled the confidence to believe the technology is ready.
“I’ve had in mind the idea AI could be used in a fundamental way for drug discovery for a very long time,” Hassabis said. “In fact, I’d say it’s the number one thing I always wanted to apply AI to once it was sophisticated enough and powerful enough.”
Backed by Alphabet, Hassabis said Isomorphic is “very well-funded for the stage that it’s at.” With over 80 employees across sites in London and Lausanne, Switzerland, the team is tapping into Alphabet’s vast computing resources, working with researchers at DeepMind, while keeping the speed and intensity of startup life.
“We’re trying to blend the best of both worlds,” he said. “All our funding comes from Alphabet to begin with, and they’re delighted with the progress it is making. That security allows us to go for the most ambitious version of the opportunity, which is to build this platform that will hopefully revolutionize the drug discovery process, as opposed to just going after one drug candidate or whatever that a lot of biotechs would do.”
Hassabis acknowledged the mountains of work ahead. Isomorphic needs a half-dozen more AlphaFold-like breakthroughs, he said.
Against that, AlphaFold feels tiny. It predicts static shapes of single proteins. But each of the trillions of cells in the human body has millions of proteins, all of which are dynamic, moving elements, interacting with countless other cellular components.
That complexity is exactly why Hassabis is so enthusiastic. He called biology “the perfect regime” for AI. In the same way that mathematics was the right language to describe physics, Hassabis sees AI as the language for biology.
“It’s very hard to imagine how you could mathematically describe a cell with a few equations,” Hassabis said. “I’ve always thought it’s the perfect place for AI to be applied. It’s turning out that way, and AlphaFold we would hold up as our proof point of that.”
For Isomorphic’s current research, Hassabis said the company is “moving up the interaction stack” in thinking about how proteins interact and bind with fellow proteins or small molecules. That may be addressable by “pushing existing methods to the limit,” he added, like using the AI techniques responsible for AlphaFold.
Isomorphic is also tackling chemistry problems, like understanding the structure of compounds, how they bind, and predicting pharmacokinetic properties. These may require completely new AI models, Hassabis said.
The goal is to build these AI systems of biology and chemistry, connect them together, and flip drug discovery upside down. Instead of starting with chemists coming up with compounds, Isomorphic wants in silico research to handle the early stages. Testing in real-world laboratories only comes as the final, confirmatory stages.
Further out, Hassabis said he hopes the company can go even further in what it can simulate.
“You might imagine a whole pathway, and eventually, maybe you can do some sort of predictive model of a cell,” Hassabis said, cautioning that a computerized cell is at least a decade away. “Then there’s organelles and organisms, at some point maybe a nematode worm or something. That would be the trajectory, and it’s very in scope for what I want Isomorphic to eventually do when we tie all our models together.”
For the near term, Isomorphic is focused on small-molecule drug development, aiming to build its own pipeline while being “open to partnerships with Big Pharma on interesting targets,” Hassabis said. In three to five years, Hassabis said he’d like to have multiple drugs in the clinic and a platform that reduces the discovery process from years to months.
The next few years will determine if AlphaFold is a one-off success story, or if Hassabis is correct in believing the time for AI in drug discovery has arrived.
“We’ve got the sweet spot just right,” Hassabis said. “You want to be five years ahead of the pack — but not 50 years ahead.” — Andrew Dunn
Maze Therapeutics: Navigating a complex Maze of technologies, rivals and targets, this startup aims big
- CEO Jason Coloma
- CMO Harold Bernstein
- Total raised $481M
- Headquarters South San Francisco, CA
Backers: Maze Therapeutics added a $150 million upfront from Sanofi recently, coming in on top of capital from Third Rock Ventures, ARCH Venture Partners, Matrix Capital Management, a16z Bio+Health, GV, General Catalyst, Casdin Capital, Woodline Partners, City Hill Ventures, Foresite Capital, Heartland Healthcare Capital, Driehaus Capital Management and several other funds.
The scoop: There aren’t a lot of players in the APOL1 field for chronic kidney disease, but the rivalry is intense. Vertex has the most advanced effort, with inaxaplin (VX-147), and an early-stage kidney drug tagged VX-840. That lead drug is in a Phase II/III trial, complete with all the bells and whistles attached to a high-profile initiative at a leading biotech. AstraZeneca also has a program in early-stage development.
But a little startup named Maze Therapeutics — now at 113 staffers — believes it’s on track to get a best-in-class player out and on the market in a high-stakes showdown.
Chronic kidney disease is viewed as an area of high unmet medical need, offering drugmakers a shot at carving out a niche in a multibillion-dollar field. But none of it is easy.
These APOL1 kidney disease patients — heavily concentrated in the African-American community in the US — have inherited risk alleles in the APOL gene that increase the rate of CKD as well as progression to end-stage kidney disease. Current treatments are less likely to be effective as well. Their therapeutic remedy is based on a protective variant — N264K — that can be used to counter the threat.
“What we were able to do at Maze then using that information about the protective variant, using a combination of structure guidance and advanced computational methods, was to develop a series of molecules that phenocopy that protective variant,” CMO Harold Bernstein says. “In fact that led to our current clinical candidate, which we’re planning to bring to the clinic later this year.”
There’s also an undisclosed drug coming up for kidney disease, for a broader spectrum of patients, which uses the same basic phenocopying approach. And it illustrates the way the whole platform works, understanding the variants and phenocopying precisely targeted new therapies for them.
“I joined Maze because of how we’re using human genetics beyond monogenic disorders and in more common diseases to design medicines,” adds the CMO, “because that’s where I think we can use this approach to have the biggest impact on human health.”
Their original lead program in Pompe disease was handed off to Sanofi last spring in a $750 million deal, after researchers gathered biomarker evidence of tackling GYS1, a known driver of the ailment, and reducing peripheral blood mononuclear cell — PBMC — glycogen. Sanofi’s team knows this field extremely well, marketing the enzyme replacement therapeutics that have for years been the only effective treatment for the disease.
Sanofi’s $150 million comes after the biotech was launched out of stealth in 2019, flush with $191 million from a syndicate led by Third Rock and ARCH — two VCs that have been openly grappling with the far less generous, post-boom biotech economy.
The startup is also now facing off against none other than Vertex in APOL1-driven CKD, and the much bigger rival is flush with cystic fibrosis money that has fueled the most advanced drug in the field. Inaxaplin is being studied in a pivotal that spurred a breakthrough drug designation by the FDA.
The Vertex team published data from a small study in the NEJM that indicates they may well be on the right track for reducing proteinuria in patients.
None of that seems to disturb anyone I talked with at Maze. Yes, says Bernstein, a Vertex vet himself, the competition has a sterling R&D rep, but that shouldn’t stop his team from excelling with a platform tech that Maze believes will come out on top in terms of drug engineering.
“When I’ve been asked why did you go to Maze — because I was at the other place for a short period of time — this was so compelling,” says Bernstein. “From my early days being more of an academic physician scientist and working at general medicines at Merck, I always felt there had to be a better way to get at these diseases. And I think that Maze is really on track for doing that.” — John Carroll
Orbital Therapeutics: A major bet on circular RNA, betting that it can upend a crowded field of startups
- CEO Giuseppe Ciaramella
- CSO Gilles Besin
- Total raised $320M
- Headquarters Cambridge, MA
Backers: The biotech raised $270 million in Series A financing led by ARCH Venture Partners alongside initial investors a16z Bio + Health and Newpath Partners. Several other groups chipped in, including Abu Dhabi Growth Fund (ADG), Redmile Group, Exor N.V., Invus, Moore Strategic Ventures, iGlobe Platinum Fund Group, Casdin Capital, Agent Capital, Alexandria Venture Investments, Rellim Capital Management, Heritage Medical Systems.
The scoop: The same year that mRNA vaccines were being put to the test against Covid-19, Howard Chang was quietly starting a company to take the genetic technology to the next level.
The Stanford geneticist was intrigued by strange and long-overlooked RNA circles in cells. Unlike their normal linear counterparts which typically only last hours, maybe a day or two tops, these circular molecules seemed extremely stable.
While the fleeting nature of mRNA worked fine for vaccines, it was causing headaches for companies that wanted to develop therapies for chronic conditions. So Chang started synthesizing circular RNAs in hopes that they might be a bit more durable. A simple experiment soon turned into a large effort to engineer and optimize the promising molecules in his lab.
“With a single dose, you can get expression for about two weeks. And this is obviously kind of like version 1.0 in academic labs,” Chang said. “Let’s say it’s a promising start.”
The work led Chang to quietly form Circ Bio in 2020. The small company soon found itself in the midst of one of the flashiest — and most heavily funded — trends in biotech. Competing startups Laronde (which has struggled amidst an internal data reproducibility crisis reported by the Boston Globe and STAT) and Orna Therapeutics raised nearly $1 billion in subsequent years based on hope that circular RNA could do everything that mRNA could do, and then some.
While Circ Bio never made it out of stealth mode, it was a formative piece of what would become Orbital, which has become a tapestry of technologies and talents with a sweeping remit to develop mRNA medicines of all stripes — both circular and stringlike.
Kristina Burow and Carol Suh from ARCH Venture Partners, the founding investor of Circ Bio, realized that scientists were barely scratching the surface of what the genetic molecule could do. It reminded them of the early days of antibody drugs, which were once scorned as impractical by Big Pharma but are now the industry’s biggest sellers. They believed mRNA was on the same trajectory.
Other biotech leaders were reaching similar conclusions, including Giuseppe Ciaramella, the president of Beam Therapeutics, which was using mRNA and lipid nanoparticles to make gene editing therapies, and John Maraganore, who recently retired after nearly 20 years at the helm of RNAi pioneer Alnylam.
The quartet founded Orbital Therapeutics, which launched last fall and announced its $270 million financing in April. The company combines Circ Bio and experimental virus-like nanoparticles from Chang’s lab with special access to the mRNA and lipid nanoparticle technologies and manufacturing capacity from Beam, which the group felt were underutilized given the company’s focus on gene editing.
“There’s no doubt in my mind that the future of medicine is going to include RNA-based approaches,” Maraganore said. “The fact that there are four or five significant players in that story right now is hardly over-saturated, when you think about the whole future of medicine and the many diseases that these types of therapies will ultimately address.”
In addition to its potential durability benefits, circular RNA appears to trigger a different kind of immune response than linear mRNA, which could be useful for some vaccine applications. Ciaramella said that Orbital is testing circular RNA “in every program that we’re doing,” but that the company is “somewhat agnostic” to which form of RNA is used in its drug candidates. “We’re just letting the science dictate which one works,” he said.
“It was clear to me that if we wanted to do this in a manner that fully optimizes the opportunity, you need to develop a very big toolbox,” said Ciaramella, who became CEO of Orbital while maintaining his post at Beam.
Orbital isn’t disclosing the specifics of its pipeline yet, but Ciaramella said that vaccines, rare disease treatments, cell therapies for cancer and immune diseases, and regenerative medicines are all on the docket. Filings for its first clinical study should come within the next few years.
Ciaramella is especially excited about the potential of mRNA medicines to encode multiple molecules, and address multiple facets of a disease, in a single injection. As an example, he envisions next-generation vaccines that provide temporary protection with expression of therapeutic antibodies while the immune system is still building its own defenses.
In addition to Chang, the company counts three other academics among its scientific founders: Stanford hematologist Ravi Majeti, UC San Diego biologist Gene Yeo, and University of Pennsylvania vaccine scientist Drew Weissman, who is one of the pioneers of mRNA vaccine technology.
Weissman, like Orbital’s other founders and leaders, seems undaunted that other companies like Moderna and BioNTech have a head start, or that other startups like Orna and ReNAgade Therapeutics have similarly broad ambitions and massive funding.
“I don’t think it makes sense to start a new RNA company that copies what Moderna or BioNTech does,” Weissman said. “But when you’ve got a brand new exciting technology that will in theory change the field, then yeah, it does.” — Ryan Cross
ReNAgade Therapeutics: Building from the ground up, in anticipation of the RNA revolution to come
- CEO Amit Munshi
- CSO Peter Smith
- Total raised $300M
- Headquarters Cambridge, MA
Backers: The launch round last spring came from a small syndicate led by its founders at MPM BioImpact and F2 Ventures.
The scoop: Ansbert Gadicke was using a custom-designed biotech blueprint when he put together a startup player called ReNAgade Therapeutics. Rather than tackle a couple of key therapies with enough money in the A round for a drive to the clinic, he wanted to mold a company that brought in multiple disciplines, weaving together technologies in a unique fashion that would give them a better chance of success — and one that would prove devilishly hard to copycat.
He’s done it one other time, with Elevate and David Hallal. And it was hands-on for Gadicke, who founded MPM Capital more than 30 years ago, from the get-go.
“I started both companies without a CEO because I felt like putting it together,” Gadicke tells me. “A little bit later, I can attract somebody who is even more advanced than on day one. In Elevate I was able to attract David Hallal, who’s obviously super well-known, and then at ReNAgade, Amit Munshi, who is similarly well-known.”
For ReNAgade, the team is following a big vision, where the future of medicine will hinge on the advance of new RNA therapies.
“I personally believe that in 10, 15 years, a third of all products in development will be RNA-based,” Gadicke says. “I personally believe it’s the same kind of wave in products as we saw 25 years ago, 30 years ago, with monoclonals. There are just such fundamental advantages in how fast it is to make a product and so on that I think that is really, to a great degree, the future.”
The money followed the vision and the plan, with a $300 million launch program put together for ReNAgade.
None of it’s going to pay off, though, without pioneers like ReNAgade tackling big challenges: challenges like half-life, expression level, product size, manufacturing and a huge obstacle for delivering next-gen RNA drugs to areas outside the liver. Get the right delivery tech together, and you would be well down the road to disrupting whole fields of medicine.
For Gadicke, the grand design called for not just building one biotech, but two. He also organized the launch of Orna, one of the leaders now in developing circular RNA as a logical next-gen approach to RNA. ReNAgade followed on the delivery side and both Gadicke startups worked together, under stealth, from a very early point.
Getting CSO Pete Smith involved early was a key part of the process. He had the luxury of having more time looking for a CEO, going with Munshi — a high-profile pick who had gained a major rep for turning Arena around and selling the company at a solid premium.
Munshi, for one, would like nothing better than building a new team that performs much like the posse of pros he had alongside him at Arena.
“We had a great team,” Munshi tells me about his previous stint. “We argued like siblings and then we had a beer after. It was just a really healthy kind of environment, and that extends to the board as well. Having that environment on the board where you can disagree, you can argue, you can debate. And you can get to the right decisions. So I don’t think the style of leadership changes.”
ReNAgade is focused on short RNA, but is more interested in long RNA right now, which Gadicke says was advantaged by the IRA legislation. And Smith had plenty of hands-on experience at key players like Moderna and Alnylam. But he was also fascinated by glycans, out of the lab of Carolyn Bertozzi, who’s co-founded a string of biotechs over the years.
“I think those two technologies can work together very well, because first of all, you can conjugate glycans to short RNA and use it directly as a delivery method, but for long RNA, you actually need to conjugate the LNPs rather than the RNA to make that work.”
This is all about technological synergy, multiplying levels of expertise into a unique R&D blend that can never easily be matched by rivals — especially in this stripped-down, asset-focused era in the post-boom world.
“Given that we have both, we can potentially improve the targeting of LNPs by putting specific glycans on top. That helps the LNP technology and we can, through the conjugation, apply the glycans to long RNA, which helps the glycan technology, so it’s really an advantage both ways.”
Biotechs like this have a lot of non-human primate research to do, and Gadicke says they developed a bar-coding tech that allowed their researchers to try multiple molecules in each monkey in their studies. And that, he adds, is giving them confidence that they can start hitting targets outside the liver.
“They did probably 10 monkey studies with quite a number of monkeys in each study, so they got a lot of data. They’re able to deliver to new cell types and organs. I need to leave it up to the company to decide when they publish those data, meaning where exactly they deliver.” — John Carroll
Seismic Therapeutic: A biotech looks for the right blend of tech — and people
- CEO Jo Viney
- CMO John Sundy
- Total raised $101M
- Headquarters Cambridge, MA
Backers: Harvard founder Tim Springer, a prolific biotech investor, got involved early in the launch of Seismic Therapeutic. The A round was led by Lightspeed Venture Partners along with the founders at Polaris Partners. GV, Boxer Capital, Samsara BioCapital joined the management team in funding the first round.
The scoop: Understanding protein structures and how they can be adapted to make better drugs has been at the core of Tim Springer’s long — and extraordinarily successful — career in founding multiple biotechs and the Institute for Protein Innovation from his perch at Harvard. So it’s not at all unusual that the growing wing of the machine-learning crowd in biotech paid careful attention to Springer’s latest creation at Seismic Therapeutic, where he and his team are looking to use the latest (and still evolving) tech to take the whole protein field into a new realm.
Joining Harvard colleague Debbie Marks, who’s been at the cutting edge of the machine learning movement in computational biology, he brought some new ideas on the technology to the attention of some longtime admirers at Polaris, which in turn lured biotech Jo Viney into the fold to helm the venture.
“Tim and Debbie had been thinking about enzymes,” Viney tells me. “I felt there was also opportunity to think about machine learning and the application to more traditional antibody discovery — how to accelerate that — and it was the merging of these two ideas that led to us with the focus of building a platform.”
Now the IMPACT platform has birthed two programs after using the tech to point them in new directions.
Many academic groups have been coming up with new machine learning applications in biology, says Viney, “but taking the tool and making a drug is the bit that still needs the drug developers.” Their special sauce: “We’re starting with the ends in mind and we’re using the best tools that we can to create the best drugs that we have using these novel technologies.”
It’s taken about 18 months to get started, from scratch, and build the first two programs, she says. And she credits the technology with shaving about a year off of the process. That will help accelerate the second 18-month phase, moving to manufacturing and getting into the clinic, as Seismic looks to vault ahead with more drugs — and quite likely a pharma alliance or two based on the interest she’s seen so far.
For Viney, it’s a first-time experience as biotech CEO, after running R&D at Pandion — which she founded — got involved in the IPO process, and then sold to Merck for $1.85 billion.
But there’s more to making a great biotech than putting new drugs into the clinic in a more efficient manner, engineering them with the latest in machine learning tech. Viney feels strongly they should build a company that relies on more “nontraditional” recruits to make a Seismic difference in biotech.
“We make sure we bring in individuals … who have different community experiences rather than the high prestige universities, people who look at things differently,” says the CEO. That can include a consideration of sexual orientation, racial contributions and more.
Do that while staying focused on hiring the best people and you can generate greater energy in the company — the kind of energy needed to create novel therapeutics. — John Carroll
Ultima Genomics: An outsider sees the $100 genome as only the beginning
- CEO Gilad Almogy
- CSO Doron Lipson
- Total raised $600M
- Headquarters Fremont, CA
Backers: General Atlantic, Andreessen Horowitz, D1 Capital, Khosla Ventures, Lightspeed, Marius Nacht, aMoon, Playground Global and Founders Fund.
The scoop: Illumina has spent years talking up the future of sequencing a genome for $100, but a secretive biotech startup led by an industry outsider quietly made it happen.
Ultima Genomics publicly launched last summer after nearly six years in stealth mode, announcing it would charge $100 per genome with its new DNA-reading technique. The company has already delivered that pricing to several early-access customers. CEO Gilad Almogy says Ultima is preparing to commercially launch “around the end of the year,” and $100 is just the beginning of its pricing ambitions.
Almogy founded Ultima in 2016, coming into healthcare after earning a PhD in physics and working in the semiconductor and solar industries. The California company’s investors, including Khosla Ventures, Lightspeed, and Andreessen Horowitz, share his tech mindset, which brought concepts from the semiconductor world to sequencing. He repeatedly invokes Moore’s law, which describes the exponential growth of the power of computer chips, as a key element of his vision.
“We built this company around the idea that for the next decades, there’s going to be this Moore’s law of data for genomics,” Almogy said. “Every time we can give twice as much data or three times as much data for the same cost, people will need five times the data.”
Illumina, the clear DNA-reading leader, played a big part in driving down the price of sequencing a genome from over $1 million to under $1,000 over the years. Just as Ultima was getting started in 2017, Illumina began talking about, one day, delivering the $100 genome. Back then, it was “almost an article of faith that you can’t take them on,” Almogy said.
But a key challenge in reaching the $100 genome has been technology. Illumina’s sequencers use flow cells, which are specialized, expensive pieces of glass used once and then thrown out.
“It’s worked for many years, but it’s kind of hit the limit of its scalability and costs,” Almogy said.
Ultima’s idea rips a page from the semiconductor playbook, using cheap silicon wafers rather than costly flow cells. DNA is placed on the wafer’s surface, which spins like a record and spreads chemicals that light up the DNA to then be read.
Asked about its technology and progress in reaching the $100 genome, an Illumina spokesperson said in a statement the company is “proud of our continued role in expanding genomic access for the widest set of users through innovation.
“Affordability of DNA sequencing is a cornerstone of Illumina’s vision of genomics for all, and the company is committed to continue pursuing a lower all-in cost per genome to increase accessibility to sequencing worldwide,” the spokesperson continued.
A few months after Ultima’s public debut, Illumina announced its newest machine, the NovaSeq X, would lower sequencing costs to $200 per genome. That’s still twice as much as Ultima, and Almogy said $100 is just the beginning for the 400-employee company.
“This is just the first step and we have to continuously drive it down,” he said. “We’re investing heavily in the next steps.”
A $100 genome is a massive milestone, but customers need to sequence thousands of genomes per year to get that pricing from Ultima, as it focuses on the world’s biggest users of sequencing.
Ultima’s vision is that cheaper sequencing can make sequencing widespread and routine. It can detect diseases earlier and customize treatment plans for more and more patients. In the long run, Almogy said he believes it will effectively become a routine lab test.
“You’ll go to your doctor every year, they draw blood, and they’ll read your DNA,” Almogy said. “There’s a zero probability of that not being the case.”
Ultima is one of several new challengers to Illumina’s sequencing dominance, with other startups like Pacific Biosciences, Element Biosciences and Singular Genomics competing for the market. Almogy said his company is already working on next-gen sequencers to build an “unsurpassable moat” that brings Moore’s law to sequencing.
“Is there a path to get from $100 to $10? Absolutely there is,” he said. “When exactly, what generation of the product, how do we get there? Those are things we’re working on and not everything we know, not everything we share. But it’s obviously doable.” — Andrew Dunn
Note: “Total raised” figures have been provided by the company or sourced from Pitchbook.vaccine treatment testing fda clinical trials preclinical genome genetic antibodies therapy monoclonal antibodies rna dna pandemic covid-19 india
Escobar: The Geopolitics Of Al-Aqsa Flood
Escobar: The Geopolitics Of Al-Aqsa Flood
Authored by Pepe Escobar via The Cradle,
Global focus just shifted from Ukraine to Palestine. This…
Global focus just shifted from Ukraine to Palestine. This new arena of confrontation will ignite further competition between the Atlanticist and Eurasian blocs. These fights are increasingly zero-sum ones; as in Ukraine, only one pole can emerge strengthened and victorious.
Hamas’ Operation Al-Aqsa Flood was meticulously planned. The launch date was conditioned by two triggering factors.
First was Israeli Prime Minister Benjamin Netanyahu flaunting his 'New Middle East' map at the UN General Assembly in September, in which he completely erased Palestine and made a mockery of every single UN resolution on the subject.
Second are the serial provocations at the holy Al-Aqsa Mosque in Jerusalem, including the straw that broke the camel’s back: two days before Al-Aqsa Flood, on 5 October, at least 800 Israeli settlers launched an assault around the mosque, beating pilgrims, destroying Palestinian shops, all under the observation of Israeli security forces.
Everyone with a functioning brain knows Al-Aqsa is a definitive red line, not just for Palestinians, but for the entire Arab and Muslim worlds.
It gets worse. The Israelis have now invoked the rhetoric of a “Pearl Harbor.” This is as threatening as it gets. The original Pearl Harbor was the American excuse to enter a world war and nuke Japan, and this “Pearl Harbor” may be Tel Aviv’s justification to launch a Gaza genocide.
Sections of the west applauding the upcoming ethnic cleansing – including Zionists posing as “analysts” saying out loud that the “population transfers” that began in 1948 “must be completed” – believe that with massive weaponry and massive media coverage, they can turn things around in short shrift, annihilate the Palestinian resistance, and leave Hamas allies like Hezbollah and Iran weakened.
Their Ukraine Project has sputtered, leaving not just egg on powerful faces, but entire European economies in ruin.
Yet as one door closes, another one opens: Jump from ally Ukraine to ally Israel, and hone your sights on adversary Iran instead of adversary Russia.
There are other good reasons to go all guns blazing.
A peaceful West Asia means Syria reconstruction – in which China is now officially involved; active redevelopment for Iraq and Lebanon; Iran and Saudi Arabia as part of BRICS 11; the Russia-China strategic partnership fully respected and interacting with all regional players, including key US allies in the Persian Gulf.
Incompetence. Willful strategy. Or both.
That brings us to the cost of launching this new “war on terror.” The propaganda is in full swing. For Netanyahu in Tel Aviv, Hamas is ISIS. For Volodymyr Zelensky in Kiev, Hamas is Russia. Over one October weekend, the war in Ukraine was completely forgotten by western mainstream media. Brandenburg Gate, the Eiffel tower, the Brazilian Senate are all Israeli now.
Egyptian intel claims it warned Tel Aviv about an imminent attack from Hamas. The Israelis chose to ignore it, as they did the Hamas training drills they observed in the weeks prior, smug in their superior knowledge that Palestinians would never have the audacity to launch a liberation operation.
Whatever happens next, Al-Aqsa Flood has already, irretrievably, shattered the hefty pop mythology around the invincibility of Tsahal, Mossad, Shin Bet, Merkava tank, Iron Dome, and the Israel Defense Forces.
Even as it ditched electronic communications, Hamas profited from the glaring collapse of Israel’s multi-billion-dollar electronic systems monitoring the most surveilled border on the planet.
Cheap Palestinian drones hit multiple sensor towers, facilitated the advance of a paragliding infantry, and cleared the way for T-shirted, AK-47-wielding assault teams to inflict breaks in the wall and cross a border that even stray cats dared not.
Israel, inevitably, turned to battering the Gaza Strip, an encircled cage of 365 square kilometers packed with 2.3 million people. The indiscriminate bombing of refugee camps, schools, civilian apartment blocks, mosques, and slums has begun. Palestinians have no navy, no air force, no artillery units, no armored fighting vehicles, and no professional army. They have little to no high-tech surveillance access, while Israel can call up NATO data if they want it.
Israeli Defense Minister Yoav Gallant proclaimed “a complete siege on the Gaza Strip. There will be no electricity, no food, no fuel, everything is closed. We are fighting human animals and we will act accordingly.”
The Israelis can merrily engage in collective punishment because, with three guaranteed UNSC vetoes in their back pocket, they know they can get away with it.
It doesn’t matter that Haaretz, Israel’s most respected newspaper, straight out concedes that “actually the Israeli government is solely responsible for what happened (Al-Aqsa Flood) for denying the rights of Palestinians.”
The Israelis are nothing if not consistent. Back in 2007, then-Israeli Defense Intelligence Chief Amos Yadlin said, “Israel would be happy if Hamas took over Gaza because IDF could then deal with Gaza as a hostile state.”
Ukraine funnels weapons to Palestinians
Only one year ago, the sweaty sweatshirt comedian in Kiev was talking about turning Ukraine into a “big Israel,” and was duly applauded by a bunch of Atlantic Council bots.
Well, it turned out quite differently. As an old-school Deep State source just informed me:
“Ukraine-earmarked weapons are ending up in the hands of the Palestinians. The question is which country is paying for it. Iran just made a deal with the US for six billion dollars and it is unlikely Iran would jeopardize that. I have a source who gave me the name of the country but I cannot reveal it. The fact is that Ukrainian weapons are going to the Gaza Strip and they are being paid for but not by Iran."
After its stunning raid last weekend, a savvy Hamas has already secured more negotiating leverage than Palestinians have wielded in decades. Significantly, while peace talks are supported by China, Russia, Turkiye, Saudi Arabia, and Egypt - Tel Aviv refuses. Netanyahu is obsessed with razing Gaza to the ground, but if that happens, a wider regional war is nearly inevitable.
Lebanon’s Hezbollah – a staunch Resistance Axis ally of the Palestinian resistance - would rather not be dragged into a war that can be devastating on its side of the border, but that could change if Israel perpetrates a de facto Gaza genocide.
Hezbollah holds at least 100,000 ballistic missiles and rockets, from Katyusha (range: 40 km) to Fajr-5 (75 km), Khaibar-1 (100 km), Zelzal 2 (210 km), Fateh-110 (300 km), and Scud B-C (500 km). Tel Aviv knows what that means, and shudders at the frequent warnings by Hezbollah leader Hassan Nasrallah that its next war with Israel will be conducted inside that country.
Which brings us to Iran.
Geopolitical plausible deniability
The key immediate consequence of Al-Aqsa Flood is that the Washington neocon wet dream of “normalization” between Israel and the Arab world will simply vanish if this turns into a Long War.
Large swathes of the Arab world in fact are already normalizing their ties with Tehran – and not only inside the newly expanded BRICS 11.
In the drive towards a multipolar world, represented by BRICS 11, the Shanghai Cooperation Organization (SCO), Eurasian Economic Union (EAEU), and China’s Belt and Road Initiative (BRI), among other groundbreaking Eurasian and Global South institutions, there’s simply no place for an ethnocentric Apartheid state fond of collective punishment.
Just this year, Israel found itself disinvited from the African Union summit. An Israeli delegation showed up anyway, and was unceremoniously ejected from the big hall, a visual that went viral. At the UN plenary sessions last month, a lone Israeli diplomat sought to disrupt Iranian President Ibrahim Raisi’s speech. No western ally stood by his side, and he too, was ejected from the premises.
As Chinese President Xi Jinping diplomatically put it in December 2022, Beijing “firmly supports the establishment of an independent state of Palestine that enjoys full sovereignty based on 1967 borders and with East Jerusalem as its capital. China supports Palestine in becoming a full member of the United Nations.”
Tehran’s strategy is way more ambitious – offering strategic advice to West Asian resistance movements from the Levant to the Persian Gulf: Hezbollah, Ansarallah, Hashd al-Shaabi, Kataib Hezbollah, Hamas, Palestinian Islamic Jihad, and countless others. It’s as if they are all part of a new Grand Chessboard de facto supervised by Grandmaster Iran.
The pieces in the chessboard were carefully positioned by none other than the late Quds Force Commander of the Islamic Revolutionary Guard Corps General Qassem Soleimani, a once-in-a-lifetime military genius. He was instrumental in creating the foundations for the cumulative successes of Iranian allies in Lebanon, Syria, Iraq, Yemen, and Palestine, as well as creating the conditions for a complex operation such as Al-Aqsa Flood.
Elsewhere in the region, the Atlanticist drive of opening strategic corridors across the Five Seas - the Caspian, the Black Sea, the Red Sea, the Persian Gulf, and the Eastern Mediterranean - is floundering badly.
Russia and Iran are already smashing US designs in the Caspian – via the International North-South Transportation Corridor (INSTC) – and the Black Sea, which is on the way to becoming a Russian lake. Tehran is paying very close attention to Moscow’s strategy in Ukraine, even as it refines its own strategy on how to debilitate the Hegemon without direct involvement: call it geopolitical plausible deniability.
Bye bye EU-Israel-Saudi-India corridor
The Russia-China-Iran alliance has been demonized as the new “axis of evil” by western neocons. That infantile rage betrays cosmic impotence. These are Real Sovereigns that can’t be messed with, and if they are, the price to pay is unthinkable.
A key example: if Iran under attack by a US-Israeli axis decided to block the Strait of Hormuz, the global energy crisis would skyrocket, and the collapse of the western economy under the weight of quadrillions of derivatives would be inevitable.
What this means, in the immediate future, is that he American Dream of interfering across the Five Seas does not even qualify as a mirage. Al-Aqsa Flood has also just buried the recently-announced and much-ballyhooed EU-Israel-Saudi Arabia-India transportation corridor.
China is keenly aware of all this incandescence taking place only a week before its 3rd Belt and Road Forum in Beijing. At stake are the BRI connectivity corridors that matter – across the Heartland, across Russia, plus the Maritime Silk Road and the Arctic Silk Road.
Then there’s the INSTC linking Russia, Iran and India – and by ancillary extension, the Gulf monarchies.
The geopolitical repercussions of Al-Aqsa Flood will speed up Russia, China and Iran’s interconnected geoeconomic and logistical connections, bypassing the Hegemon and its Empire of Bases. Increased trade and non-stop cargo movement are all about (good) business. On equal terms, with mutual respect - not exactly the War Party’s scenario for a destabilized West Asia.
Oh, the things that a slow-moving paragliding infantry overflying a wall can accelerate.
* * *
The views expressed in this article do not necessarily reflect those of The Cradle or ZeroHedge.
Visualizing All Attempted & Successful Moon Landings
Visualizing All Attempted & Successful Moon Landings
Since before Ancient Greece and the first Chinese Dynasties, people have sought to…
Since before Ancient Greece and the first Chinese Dynasties, people have sought to understand and learn more about the moon.
Curiosity and centuries of study culminated in the first moon landing in the 1960s. But there have been many other attempted moon landings, both before and after.
Race to the Moon
The 1960s and 1970s marked an era of intense competition between the U.S. and the Soviet Union as they raced to conquer the moon.
During the Cold War, space became a priority as each side sought to prove the superiority of its technology, its military firepower, and its political-economic system.
In 1961, President John F. Kennedy set a national goal to have a crewed lunar landing and return to Earth.
After several failed attempts from both sides, on July 20, 1969, the Apollo 11 mission was successful and astronauts Neil Armstrong and Buzz Aldrin became the first humans to set foot on the moon.
|Mission||Launch Date||Operator||Country||Mission Type||Outcome|
|Ranger 3||26-Jan-62||NASA||???????? U.S.||Lander||Spacecraft failure|
|Ranger 4||23-Apr-62||NASA||???????? U.S.||Lander||Spacecraft failure|
|Ranger 5||18-Oct-62||NASA||???????? U.S.||Lander||Spacecraft failure|
|Luna E-6 No.2||4-Jan-63||OKB-1||☭ USSR||Lander||Launch failure|
|Luna E-6 No.3||3-Feb-63||OKB-1||☭ USSR||Lander||Launch failure|
|Luna 4||2-Apr-63||OKB-1||☭ USSR||Lander||Spacecraft failure|
|Luna E-6 No.6||21-Mar-64||OKB-1||☭ USSR||Lander||Launch failure|
|Luna E-6 No.5||20-Apr-64||OKB-1||☭ USSR||Lander||Launch failure|
|Kosmos 60||12-Mar-65||Lavochkin||☭ USSR||Lander||Launch failure|
|Luna E-6 No.8||10-Apr-65||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 5||9-May-65||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 6||8-Jun-65||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 7||4-Oct-65||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 8||3-Dec-65||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 9||31-Jan-66||Lavochkin||☭ USSR||Lander||Successful|
|Surveyor 1||30-May-66||NASA||???????? U.S.||Lander||Successful|
|Surveyor 2||20-Sep-66||NASA||???????? U.S.||Lander||Spacecraft failure|
|Luna 13||21-Dec-66||Lavochkin||☭ USSR||Lander||Successful|
|Surveyor 3||17-Apr-67||NASA||???????? U.S.||Lander||Successful|
|Surveyor 4||14-Jul-67||NASA||???????? U.S.||Lander||Spacecraft failure|
|Surveyor 5||8-Sep-67||NASA||???????? U.S.||Lander||Successful|
|Surveyor 6||7-Nov-67||NASA||???????? U.S.||Lander||Successful|
|Surveyor 7||7-Jan-68||NASA||???????? U.S.||Lander||Successful|
|Luna E-8 No.201||19-Feb-69||Lavochkin||☭ USSR||Lander||Launch failure|
|Luna E-8-5 No.402||14-Jun-69||Lavochkin||☭ USSR||Lander||Launch failure|
|Luna 15||13-Jul-69||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Apollo 11||16-Jul-69||NASA||???????? U.S.||Lander/
|Kosmos 300||23-Sep-69||Lavochkin||☭ USSR||Lander||Launch failure|
|Kosmos 305||22-Oct-69||Lavochkin||☭ USSR||Lander||Launch failure|
|Apollo 12||14-Nov-69||NASA||???????? U.S.||Lander/
|Luna E-8-5 No.405||6-Feb-70||Lavochkin||☭ USSR||Lander||Launch failure|
|Apollo 13||11-Apr-70||NASA||???????? U.S.||Lander/
|Luna 16||12-Sep-70||Lavochkin||☭ USSR||Lander||Successful|
|Luna 17||10-Nov-70||Lavochkin||☭ USSR||Lander||Successful|
|Apollo 14||31-Jan-71||NASA||???????? U.S.||Lander/
|Apollo 15||26-Jul-71||NASA||???????? U.S.||Lander/
|Luna 18||2-Sep-71||Lavochkin||☭ USSR||Lander||Spacecraft failure|
|Luna 20||14-Feb-72||Lavochkin||☭ USSR||Lander||Successful|
|Apollo 16||16-Apr-72||NASA||???????? U.S.||Lander/
|Apollo 17||7-Dec-72||NASA||???????? U.S.||Lander/
|Luna 21||8-Jan-73||Lavochkin||☭ USSR||Lander||Successful|
|Luna 23||16-Oct-75||Lavochkin||☭ USSR||Lander||Partial failure|
|Luna E-8-5M No.412||16-Oct-75||Lavochkin||☭ USSR||Lander||Launch failure|
|Luna 24||9-Aug-76||Lavochkin||☭ USSR||Lander||Successful|
|Chang'e 3||1-Dec-13||CNSA||???????? China||Lander||Operational|
|Chang'e 4||7-Dec-18||CNSA||???????? China||Lander||Operational|
|Beresheet||22-Feb-19||SpaceIL||???????? Israel||Lander||Spacecraft failure|
|Chandrayaan-2||22-Jul-19||ISRO||???????? India||Lander||Spacecraft Failure|
|Chang'e 5||23-Nov-20||CNSA||???????? China||Lander||Successful|
|Hakuto-R Mission 1||11-Dec-22||ispace||???????? Japan||Lander||Spacecraft failure|
|Luna 25||10-Aug-23||Roscosmos||???????? Russia||Lander||Spacecraft failure|
After the Apollo missions, the fervor of lunar exploration waned. From 1976 to 2013, no moon landing attempts occurred due to budget constraints, shifting priorities, and advances in robotic missions.
However, a new chapter in space exploration has unfolded in recent years, with emerging players entering the cosmic arena. With its Chang’e missions, China has made significant strides, landing rovers on the moon and exploring the far side of the moon.
India, too, has asserted its presence with the Chandrayaan missions. In 2023, the country became the 4th nation to reach the moon as an unmanned spacecraft landed near the lunar south pole, advancing the country’s space ambitions to learn more about the lunar ice, potentially one of the moon’s most valuable resources.
Exploring Lunar Water
Since the 1960s, even before the historic Apollo landing, scientists had theorized the potential existence of water on the moon.
In 2008, Brown University researchers employed advanced technology to reexamine lunar samples, discovering hydrogen within beads of volcanic glass. And in 2009, a NASA instrument aboard the India’s Chandrayaan-1 probe confirmed the presence of water on the moon’s surface.
Water is deemed crucial for future space exploration. Beyond serving as a potential source of drinking water for future moon explorations, ice deposits could play a pivotal role in cooling equipment. Lunar ice could also be broken down to produce hydrogen for fuel and oxygen for breathing, essential for supporting extended space missions.
With a reinvigorated interest in exploring the moon, manned moon landings are on the horizon once again. In April 2023, NASA conducted tests for the launch of Artemis I, the first American spacecraft to aim for the moon since 1972. The agency aims to send astronauts to the moon around 2025 and build a base camp on the lunar surface.
“We Can’t Force The Human Body To Accept Foreign Genetic Code” Dr. McCullough On mRNA Technology
"We Can’t Force The Human Body To Accept Foreign Genetic Code” Dr. McCullough On mRNA Technology
Authored by Naveen Athrappully via The Epoch…
Authored by Naveen Athrappully via The Epoch Times (emphasis ours),
Cardiologist Dr. Peter McCullough warned that messenger RNA (mRNA) vaccines inject “foreign genetic code” into human beings, which the body fails to break down or expel for a prolonged period of time.
Research on mRNA “has been going on for decades,” Dr. McCullough said during an Oct. 5 interview. The 2023 Nobel Prize for medicine was awarded to two scientists for making “messenger RNA long-lasting in the human body,” he said. “I mean, it has been tested in multiple applications … It's an absolute bust. It was just the worst idea ever to install the genetic code for a lethal protein without being able to shut it off. It wasn't the fact that it was rushed; it's just ill-conceived from the very beginning.”
“We can't force the human body to accept foreign genetic code and produce a foreign protein … Messenger RNA for vaccines is a completely failed concept. It’s a dangerous concept, and the U.S. government wasn't honest. They should have been honest. Trump should have come out and said, ‘Listen, it's on our website; our military's been working on this since 2012.’”
During a testimony at the European Parliament last month, Dr. McCullough said, “There's not a single study showing that the messenger RNA is broken down” in the human body once it is injected.
“There's not a study showing it leaves the body.” Since the vaccines are “made synthetically, they cannot be broken down.”
He added that the lethal protein from the [COVID-19] vaccines found in the human body after vaccination was found to be circulating “at least for six months, if not longer.”
In the case of seasonal jabs, that is, taking an injection or booster at the end of six months as recommended by the authorities, “there's another installation in more circulating potentially lethal protein.”
Scientist Drew Weissman, who won the 2023 Nobel Prize in Medicine for his role in developing mRNA technology, warned in a 2018 paper that not only did clinical trials of mRNA vaccines produce “more modest [results] in humans than was expected based on animal models,” but that the “side effects were not trivial.”
Dr. Mccullough’s comments come as the Gates Foundation is spending $40 million on countries in Africa and other economically backward nations to produce new mRNA vaccines in efforts to prevent diseases like tuberculosis and malaria.
Concealing a ‘Global Security Threat’
In the Steve Deace interview, Dr. McCullough said that the ineffectiveness of the technology was not unknown to the government since they’ve been testing it for nearly 40 years.
He referred to a February 2023 paper published in the British Medical Journal (BMJ), which cited that the U.S. government has been investing billions of dollars in developing messenger RNA technology since 1985.
The Defense Advanced Research Projects Agency (DARPA) began investing in mRNA tech in 2011. DARPA then launched the Pandemic Prevention Platform (P3) program in 2016 that sought to produce “relevant numbers of doses” against infections within 60 days of identifying them.
The ADEPT P3 was a program by the U.S. military “to end pandemics in 60 days.” There is no other technology “that our government has invested more in,” Dr. McCullough said.
Dr. McCullough cited another paper that stated there were “over 9,000 patents on messenger RNA. And all the patent assignees are big entities. At the top is Sanofi, then Cervavac, BioNTech, Moderna, and the U.S. government. No single person invented messenger RNA. Someone who comes up in 2021 and says, ‘You know I invented it’. That's impossible. This has been going on for decades.”
Dr. McCullough pointed out that the United States and China have been in “collaboration for years” in their research on infectious and lethal coronavirus.
However, officials like Anthony Fauci, the former head of the National Institutes of Allergy and Infectious Diseases (NIAID), Francis Collins, the former head of the National Institutes of Health (NIH), and “a whole cadre of scientists, they collaborated to conceal this global security threat.”
“They actually intentionally lied to the world and said the virus came out of nature. They knew it came out of the Wuhan lab,” he said, citing a research paper by Ralph Baric and Dr. Zhengli-Li Shi that was published in the Nature journal in 2015.
Dr. Zhengli-Li Shi is affiliated with the Wuhan Institute of Virology, while Mr. Baric is from the Department of Epidemiology, University of North Carolina at Chapel Hill.
“They said they created SARS-CoV-2 virus. They called it the Wuhan Institute of Virology 1 virus. That was the prototype SARS-CoV-2. So, that's in 2015. Instead of bringing Ralph Baric out [and asking] ‘Dr. Baric, how do we get ourselves out of this disaster,’ you masterminded this virus funded by the US.”
‘Pull All COVID-19 Vaccines Off the Market’
In his interview, Dr. McCullough made three recommendations. “I say number one, I've called in the US Senate [and] now the European Parliament [to] pull all COVID-19 vaccines off the market before anyone else is harmed.”
“Number two, US, EU and all westernized Nations [should] pull out of the WHO. They're not trustable. And number three, I'm following the World Council for Health. I am recommending a halt on all childhood vaccines, the entire vaccine schedule until this is clarified since messenger RNA is now on the schedule without any concerns for safety.
While some studies related to the safety of COVID-19 vaccines have shown the jabs to be safe, others have raised concerns about the safety of the shots.
A December 2022 study analyzed trials comparing vaccine recipients with individuals who did not receive a vaccine or were given a placebo.
It concluded that “compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease.”
However, a June 2022 study that looked at mRNA vaccinations found that “Pfizer and Moderna mRNA COVID-19 vaccines were associated with an increased risk of serious adverse events of special interest (AESI).”
“The excess risk of serious adverse events of special interest surpassed the risk reduction for COVID-19 hospitalization relative to the placebo group in both Pfizer and Moderna trials.”
‘Shedding’ the Infection
During the interview, Mr. Deace asked about hearing issues that he and his colleague suffered and whether they had any ties with the vaccines. While he did not take a COVID-19 shot, the colleague was vaccinated. Mr. Deace asked if this was “further proof that basically the last few years Peter everybody was a lab rat whether you took the vaccine or not.”
“It's true, nearly all of us have been exposed to the Wuhan spike protein,” Dr. McCullough replied. “When I see patients in the office, we check antibodies against the spike protein. Invariably, they're elevated. Rarely, I'll find somebody who hasn't been exposed.”
Dr. McCullough pointed out that there are “clear-cut papers” showing individuals suffering hearing loss after taking COVID-19 jabs. “It's all related to the spike protein,” he said. mRNA vaccines work by instructing cells in the body to produce the spike protein found on the surface of the COVID-19 virus.
Once vaccinated, an individual’s muscle cells begin producing spike protein pieces, displaying them on cell surfaces, which end up triggering the immune system to create antibodies. When such an individual gets infected with the COVID-19 virus, these antibodies will then fight the virus.
Dr. McCullough warned that even people who have not received mRNA COVID-19 vaccines can eventually get affected by messenger RNA through a vaccinated individual via “shedding.”
“Shedding means that one has been exposed to the spike protein or to the messenger RNA from close contact with another individual. We know both of them can travel via exosomes which are small phospholipid packets that can be exhaled [via] breath, through sweat, [and] various forms of body fluid, typically you know very close contact.”
“There was a big project called the Eva project in the UK showing 78 percent of women who take a vaccine—they actually have menstrual abnormalities. And those who even didn't take a vaccine, they end up having menstrual abnormalities. There's been plenty of these reports that have occurred.”
Dr. McCullough cited an interview he did with scientist Helene Banoun, an expert on shedding, who believes such things “clearly happens, for sure, in people who've taken the vaccine within 30 days, close contact.”
“Now, two studies—one in the United States, one in Japan—[show] the messenger RNA comes through breast milk. The spike protein may be shedded potentially for a much longer duration of time. It's been shown in the human body now for months, maybe even years afterward. And that's the rationale for what our recent proposal to actually undergo spike protein detoxification.”
The cardiologist pointed out that “every signal” related to cardiovascular disease, neurologic disease, blood clots, immune disease, and cancer “is up.”
“There can be debates on why all these chronic diseases are up, all-cause mortality up in every single area of the world,” he said. “The two big exposures we've had are COVID-19 infection and now COVID-19 vaccines, and I think both mechanisms have led to this wave of disease.”
“I think more powerfully with the vaccines since the vaccines are largely genetic, they're given every six months, and they install the genetic code for the disease-promoting and lethal Wuhan spike protein.”
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