Novartis manufacturing associate checking punches at compressing machine.
Source: Novartis
In 2010, a volcano erupted in Iceland. For Dr. Oliver Sartor, a cancer research professor at the Tulane University School of Medicine, it was a problem.
Ash from the eruption disrupted flights across Europe — including a time-sensitive shipment of experimental radioligand therapy that Sartor was expecting from Norway.
Radioligand therapy, also called radionuclide or radiopharmaceutical therapy, is a targeted form of cancer treatment that delivers radiation directly to cancer cells. While other forms of cancer treatment can target any rapidly dividing cells in the body, radioligand therapy’s precision helps limit damage to healthy, surrounding tissue.
It’s an effective form of treatment that many experts and patients are excited about, but there’s a significant catch — the medication expires within days after it’s manufactured.
A radioligand is made of a radioisotope, which emits radiation that damages cells, and a targeted ligand — a molecule that binds to specific markers on cancer cells. The radioactive component has a very short half-life, or the time it takes for the radioactivity to decrease by 50%. Once the radioactivity decays, it can no longer kill the cancer cells as effectively, which means radioligand therapy has a limited window of viability. By the time it is packaged and ready to ship, the treatment has to reach patients in a matter of days.
“It takes planning,” Sartor told CNBC. “It’s not something you just sort of walk in and say ‘Oh, I think I’ll give you [this] today.'”
Pharmaceutical company Novartis believes the returns will be worth the challenge of mastering this race against time.
Novartis currently produces two radioligand therapy treatments called Lutathera, which treats neuroendocrine tumors, a rare form of cancer in the digestive tract, and Pluvicto, for patients with a specific type of prostate cancer. They were both approved by the Food and Drug Administration.
As of October, Novartis had treated more than 16,000 neuroendocrine patients and 4,000 prostate cancer patients in the U.S. Pluvicto was approved only last March and demand is increasing. As many as 60,000 U.S. patients could ultimately benefit from the medicine, said Jeevan Virk, head of radioligand therapy at Novartis.
The drugs are expensive. The list price (wholesale acquisition cost) of Pluvicto is around $42,500, while Lutathera is around $53,200, and most patients require between four to six doses. Novartis, which generated more than $50 billion in net sales last year, believes Pluvicto holds multibillion-dollar peak sales potential.
But in order to realize that potential, Novartis has to move the medication through the supply chain seamlessly.
Expensive to produce and ship fast
Nuclear medicine has been used to treat cancer for decades, and radioligand therapy itself is not new. The therapy has previously been used to treat cancers like lymphoma, but it was not always widely accepted or used by members of the medical community.
“I think it was challenging for it to find its place,” said Dr. Delphine Chen, director of molecular imaging and therapy at Fred Hutchinson Cancer Center in Seattle.
Dr. Leo I. Gordon, a professor of cancer research at Northwestern University’s Feinberg School of Medicine, said the hesitation often comes down to finances.
Producing radioligand therapy is expensive, and companies have to be willing to shoulder the costs and navigate a challenging supply chain in the hope that they can eventually make a profit.
“I’m not sure it’s a great message to send that everything is based on profit mode and all,” he said, “but it certainly does exist in medicine, oncology and the world.”
For lymphoma, it’s not a long-term investment any company has been willing to make, Gordon said. But since Pluvicto and Lutathera outperform existing treatments available for certain prostate and neuroendocrine cancers, they are being seen to have significant commercial promise.
“There’s a lot of excitement around it,” said Chen, who has administered both drugs to patients. “A lot of patients feel better on it, so that’s really exciting and gratifying to me as a physician to be able to offer something that actually is helpful with minimal toxicity.”
Novartis engineers in packaging facility.
Source: Novartis
Novartis manufactures radioligand therapy at three sites in Italy, Spain and New Jersey, and has a fourth facility slated to open in Indiana next year. Virk said between 70 to 150 people work in each facility, and the site in Indiana will be Novartis’ largest to date.
For both Pluvicto and Lutathera, the manufacturing process begins with a mineral. The minerals are enriched into a stable isotope and exposed to radiation in nuclear reactors, where they ultimately become radioactive after around two to three weeks. During the irradiation, the enriched isotopes are placed into capsules to keep them secure.
The strength of the radiation starts to decay as soon as the capsules are taken out of the reactors, which means Novartis begins a race against a ticking clock. The radioactive atoms have a half-life of just six and a half days.
The capsules are transferred to an isotope-precursor production facility where they are further purified and concentrated into a radioactive liquid salt solution. At the end of this stage, which takes around 48 hours, there is enough radioactivity in one vial to treat between 30 and 50 patients.
The final step takes place in a labeling facility where the radioactive atoms are attached to targeting molecules, or the medicine itself, and that takes around 24 hours. After the final product has been packaged and inspected for quality, it is ready to be shipped.
The drugs have different shelf lives depending on how much radiation Novartis can load into one vial. Pluvicto expires five days after it’s packaged at the factory, while Lutathera has a 72-hour shelf life.
“We basically need to get the product distributed around the world, just in 72 hours, from those three production sites,” Virk said. “This includes anywhere from Tokyo to Anchorage, so it’s an incredible distance that needs to be covered.”
Novartis scientist in lab packing materials for transportation.
Source: Novartis
Pluvicto and Lutathera are packaged inside a small lead container, roughly the size of a credit card. Lead is a strong insulator, so it doesn’t allow the radiation to escape. The drugs are also placed inside an additional container called a Type-A container, which is made of Styrofoam and helps with temperature control.
The risk of radiation exposure is so minimal that radioligand therapy is often transported via commercial airlines and cargo planes. When doses have to be transported on the ground, Virk said Novartis often uses a private courier van service to ensure they reach their destination as quickly as possible.
The process is timed to the minute, said Virk, and there’s a team of around 30 to 40 people at Novartis who oversees the complex logistics.
“It’s a 24/7 operation as you might imagine, because we really have customers around the globe that depend on ensuring that patients get their doses,” he said. “That’s really the fuel that keeps us going.”
Mistakes can happen, and things do go wrong in the supply chain occasionally, Virk said. But errors are costly, because if the shipments do not reach patients in time, the doses can’t be salvaged, and the manufacturing process has to start over.
Patients feel the difference
Radioligand therapy is administered through an IV infusion, and though it does help limit damage to healthy tissue, patients can experience some side effects.
Chen of the Fred Hutchinson Cancer Center said patients who receive Pluvicto can experience some nausea, vomiting, diarrhea, constipation, and fatigue in the short term. “Most of them have had only mild nausea that we’ve observed, and so Pluvicto is very well tolerated compared to chemotherapy,” she said.
Chen said patients can experience many of the same symptoms with Lutathera, but the diarrhea can be exacerbated, and some patients contend with worsening bowel obstruction. In rare cases, patients may be unable to maintain their blood pressure.
But for many patients, these side effects are worth it.
Vanue Lacour Jr. was first diagnosed with prostate cancer in 2007, and underwent a “tough” surgery to remove his prostate after his diagnosis. He stayed cancer-free for eight years, but in 2015, he learned he had relapsed with an advanced form of prostate cancer that had spread into his bones.
“I was determined to win,” the 80-year-old told CNBC. “I’m determined to live.”
Lacour began a grueling round of chemotherapy that he described as a “very, very hard, harsh medicine.” He incurred painful damage to nerves in his foot and leg that he still lives with today.
The chemotherapy helped stabilize his cancer, but Lacour said his doctors were not satisfied. In 2018, Lacour enrolled in a clinical trial for Pluvicto and received six doses over eight months. Now, he is officially in remission.
“I had no real side effects,” Lacour said. “I’m getting back to doing a lot of the things I like to do.”
Radioligand therapy has also helped Josh Mailman, who learned he had a softball-sized neuroendocrine tumor of the pancreas in 2007. The cancer had also spread to his liver.
“I didn’t know how much time I had,” the 61-year-old Oakland, California, resident told CNBC. “There were very few treatments for pancreatic neuroendocrine tumors at the time.”
Mailman decided to join a support group, and he said the other members encouraged him to learn as much as possible about his disease. In 2008, he traveled to a medical conference in Toronto where he heard about radioligand therapy for the first time. As his symptoms worsened over the next six months, his doctor agreed to give Mailman his first dose of radioligand therapy under compassionate care in 2009.
Mailman received three doses of radioligand therapy in 2009 and 2010, and he said it kept his cancer stable for the next six years. He has since had two follow-up treatments — one in 2016 and one in 2020, after the FDA approved Lutathera.
“I’m still here 15 years later,” he said. “It’s been a game-changer in the neuroendocrine tumor space.”
Because of his success with radioligand therapy, Mailman has become deeply involved in patient advocacy, where he works to raise awareness about nuclear medicine and neuroendocrine tumors.
“I would say I’m retired, my wife disagrees,” Mailman joked.
Mailman also runs virtual patient groups twice a week, where patients, friends and family members can come together to discuss their diagnosis and treatments. Mailman said radioligand therapy is discussed in more than 90% of the sessions.
“Either someone’s going to have it, someone had it, someone wants to know more about it,” he said.
During one session CNBC observed in early November, more than a dozen patients met and discussed their experiences with and concerns about radioligand therapy. Patients who had already received it answered questions about their side effects and shared tips about how to overcome fear about needles and radiation.
It is common for patients to express unease about the radiation, said Chen, but there are clear precautions in place to limit exposure and protect others.
Completion was expected in the second half of next year, the Swiss pharma group said.
Arnd Wiegmann | Reuters
The road ahead
As demand for radioligand therapy increases, Novartis’ challenge is to scale up access and awareness about the medication.
Virk, head of radioligand therapy at Novartis, said the company is working with health care systems, governments and other regulatory agencies around the world to improve its operations.
“From my perspective, [radioligand therapy] as a platform is still very much in its infancy,” he said. “So [we’re] really excited about the drug, [but] very acutely aware that we’re just at the beginning of this radioligand therapy revolution.”
Sartor at the Tulane University School of Medicine said there is still work to be done, particularly in terms of optimizing the supply chain but that radioligand therapy makes a real difference for patients.
“I think radioligand therapy has arrived in a way that is meaningful for patients today,” he said. “I’m anxious for patients to be able to receive the therapy in an FDA-approved manner, and also to do the next generation of clinical trials to ensure that even more people will have access in the future.”
Nvidia CEO Jensen Huang in Taipei, Taiwan, on June 2, 2024.
Ann Wang | Reuters
Nvidia’s Blackwell Ultra chips, the company’s next-generation graphics processor for artificial intelligence, have been commercially deployed at CoreWeave, the companies announced on Thursday.
CoreWeave has received shipments of Dell-built shipments based around Nvidia’s GB300 NVL72 AI systems, Dell said on Thursday. It’s the first cloud provider to install systems based around Blackwell Ultra.
The Blackwell Ultra is Nvidia’s latest chip, expected to ship in volume during the rest of the year. The systems that CoreWeave is installing are liquid-cooled and include 72 Blackwell Ultra GPUs and 36 Nvidia Grace CPUs. The systems are assembled and tested in the U.S., Dell said.
CoreWeave shares rose 6% during trading on Thursday, Dell shares were up about 2% and Nvidia rose less than 2%.
The announcement is a milestone for Nvidia.
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AI developers still clamor for the latest Nvidia chips, which have improvements that make them better for training and deploying models.
Nvidia said Blackwell Ultra can produce 50 times more AI content than its predecessor, Blackwell.
Investors closely watch how Nvidia manages the transition when it announces new AI chips to see if there are production issues or delays. Nvidia CFO Colette Kress said in May that Blackwell Ultra shipments would start in the current quarter.
It’s also a win for CoreWeave, a cloud provider that rents access to Nvidia GPUs to other clouds and AI developers. Although CoreWeave is smaller than the cloud services operated by Amazon, Google, and Microsoft, its ability to offer Nvidia’s latest chips first give it a way to differentiate itself.
CoreWeave historically has a close relationship with Nvidia, which owns a stake in the cloud provider. CoreWeave went public earlier this year, and the stock price has quadrupled since its IPO.
Jeremy Allaire, CEO and co-founder of Circle Internet Group, the issuer of one of the world’s biggest stablecoins, and Circle Internet Group co-founder Sean Neville react as they ring the opening bell, on the day of the company’s IPO, in New York City, U.S., June 5, 2025.
NYSE
For over three years, venture capital firms have been waiting for this moment.
Tech IPOs came to a virtual standstill in early 2022 due to soaring inflation and rising interest rates, while big acquisitions were mostly off the table as increased regulatory scrutiny in the U.S. and Europe turned away potential buyers.
Though it’s too soon to say those days are entirely in the past, the first half of 2025 showed signs of momentum, with June in particular producing much-needed returns for Silicon Valley’s startup financiers. In all, there were five tech IPOs last month, accelerating from a monthly average of two since January, according to data from CB Insights.
Highlighting that group was crypto company Circle, which more than doubled in its New York Stock Exchange debut on June 5, and is now up sixfold from its IPO price for a market cap of $42 billion. The stock got a big boost in mid-June after the Senate passed the GENIUS Act, which would establish a federal framework for U.S. dollar-pegged stablecoins.
Venture firms General Catalyst, Breyer Capital and Accel now own a combined $8 billion worth of Circle stock even after selling a fraction of their holdings in the offering. Silicon Valley stalwarts Greylock, Kleiner Perkins and Sequoia Capital are set to soon profit from Figma’s IPO, after the design software vendor filed its public prospectus on Tuesday. Since its $20 billion acquisition agreement with Adobe was scrapped in late 2023, Figma has been one of the most hotly anticipated IPOs in startup land.
It’s “refreshing and something that we’ve been waiting for for a long time,” said Eric Hippeau, managing partner at early-stage venture firm Lerer Hippeau, regarding the exit environment. “I’m not sure that we are confident that this can be a sustained trend yet, but it’s been very encouraging.”
Another positive sign for the industry the past couple months was the performance of artificial infrastructure provider CoreWeave, which went public in late March. The stock was relatively stagnant for its first month on the market but shot up 170% in May and another 47% in June.
For venture firms, long considered the lifeblood of risky tech startups, IPOs are essential in order to generate profits for the university endowments, foundations and pension funds that allocate a portion of their capital to the asset class. Without handsome returns, there’s little incentive for limited partners to put money into future funds.
After a record year in 2021, which saw 155 U.S. venture-backed IPOs raise $60.4 billion, according to data from University of Florida finance professor Jay Ritter, every year since has been relatively dismal. There were 13 such offerings in 2022, followed by 18 in 2023 and 30 last year, collectively raising $13.3 billion, Ritter’s data shows.
The slowdown followed the Federal Reserve’s aggressive rate-hiking campaign in 2022, meant to slow crippling inflation. As the lower-growth environment extended into years two and three, venture firms faced increasing pressure to return cash to investors.
‘Backlog of liquidity’
In its 2024 yearbook, the National Venture Capital Association said that even with a 34% increase in U.S. VC exit value last year to $98 billion, that number is 87% below the 2021 peak and less than half the average for the four years from 2017 through 2020. It’s a troubling dynamic for the 58,000 venture-backed companies that have raised a total of $947 billion from investors, according to the annual report, which is produced by the NVCA and PitchBook.
“This backlog of liquidity drought risks creating a ‘zombie company’ cohort — businesses generating operational cash flow but lacking credible exit prospects,” the report said.
Other than Circle, the latest crop of IPOs mostly consists of smaller and lesser-known brands. Health-tech companies Hinge Health and Omada Health are valued at about $3.5 billion and $1 billion, respectively. Etoro, an online trading platform, has a market cap of just over $5 billion. Online banking provider Chime Financial has a higher profile due largely to a years-long marketing blitz and is valued at close to $11.5 billion.
Meanwhile, the highest valued private companies like SpaceX, Stripe and Databricks remain on the sidelines, and AI highfliers OpenAI and Anthropic continue to raise massive amounts of cash with no intention of going public anytime soon.
Still, venture capitalists told CNBC that there are plenty of companies with the financial metrics to be public, and that more of them are readying for the process.
“The IPO market is starting to open and the VC world is cautiously optimistic,” said Rick Heitzmann, a partner at venture firm FirstMark in New York. “We are preparing companies for the next wave of public offerings.”
There are other ways to make money in the meantime. Secondary sales, a process that involves selling private shares to new investors, are on the rise, allowing early employees and investors to get some liquidity.
And then there’s what Mark Zuckerberg is doing, as he tries to position his company at the center of AI innovation and development.
Mark Zuckerberg, chief executive officer of Meta Platforms Inc., during the Meta Connect event on Wednesday, Sept. 25, 2024.
Bloomberg | Bloomberg | Getty Images
Last month, Meta announced a $14 billion bet on Scale AI, taking a 49% stake in the AI startup in exchange for poaching founder Alexandr Wang and a small group of his top engineers. The deal effectively bought out half of the stock owned by investors, leaving them with the opportunity to make money on the rest of their holdings, should a future acquisition or IPO take place.
The deal is a big win for Accel, which led Scale AI’s Series A round in 2017, and is poised to earn more than $2.5 billion in the transaction. Index Ventures led the Series B in 2018, and Peter Thiel’s Founders Fund led the Series C the following year at a valuation of over $1 billion.
Investors now hope the Federal Reserve will move toward a rate-cutting campaign, though the central bank hasn’t committed to one. There’s also ongoing optimism that regulators will make going public less burdensome. Last week, Reuters reported, citing sources familiar with the matter, that U.S. stock exchanges and the SEC have discussed loosening regulations to make IPOs more enticing.
Mike Bellin, who heads consulting firm PwC’s U.S. IPO practice, said he anticipates a diversity of IPOs across sectors in the second half of the year. According to data from PwC, pharma and fintech were among the most active sectors for deals through the end of May.
While the recent trend in IPO activity is an encouraging sign for investors, potential roadblocks remain.
Tariffs and geopolitical uncertainty delayed IPO plans from companies including Klarna and StubHub in April. Neither has provided an update on when they plan to debut.
FirstMark’s Heitzmann said the path forward is “not at all clear,” adding that he wants to see a strong quarter of economic stability and growth before confidently saying that the market is wide open.
Additionally, other than CoreWeave and Circle, recent tech IPOs haven’t had big pops. Hinge Health, Chime and eToro have seen relatively modest gains from their offer price, while Omada Health is down.
But virtually any activity beats what VCs were experiencing the last few years. Overall, Hippeau said recent IPO trends are generally encouraging.
“There’s starting to be kind of light at the end of the tunnel,” Hippeau said.
The position was valued at about $160 million as of Wednesday’s close.
Tripadvisor shares have been flat since the start of the year after plummeting more than 30% in 2024. Last year, the travel review and booking company said it created a special committee to explore potential options.
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Starboard Value has gained a reputation for pushing for changes such as new CEOs and cost cuts by acquiring significant shares in companies.