STAT+: Ophthalmology venture grabs investors’ attention, raises $330 million
A startup developing treatments for eye diseases has raised $330 million from investors as it readies for late-stage testing.
Ollin Biosciences is about to begin a Phase 3 trial of a treatment for both diabetic macular edema and wet age-related macular degeneration. The conditions affect millions of Americans and can lead to vision loss.
Ahead of the trial, Ollin told STAT it had raised the Series B funding from an assortment of established biotech investors, a pension fund, and even crossover investors — a breed of private investors who will take a stake in a company shortly before it moves over to the stock market. TCGX and ARCH Venture Partners co-led the funding round, which was one of the largest Series B rounds for a biotech company in the last two years.
California Still Golden Despite Job Losses: Industry Group
SAN DIEGO—California’s three life sciences clusters all lost jobs last year, yet the industry remains a major engine of innovation and economic growth, according to a report released by the state’s largest life sciences organization to coincide with the Biotechnology Industry Organization (BIO) International Convention being held here.
BIOCOM California quantified the economic impact of the Golden State’s life sciences industry as generating $394 billion in economic output in 2025—a figure that goes beyond the direct impact of the 406,505 people employed by life sciences employers across the state. The impact figure includes indirect impact (activity generated through suppliers, vendors, and subcontractors supporting the industry) and induced impact (the household spending generated by workers employed in both life-sci organizations and supporting industries).
When indirect and induced impact are accounted for, the life sciences sustain 1,079,365 jobs statewide, the report stated.
However, all three of the state’s top-tier life-sci clusters—the San Francisco Bay Area, San Diego, and the Los Angeles/Orange County region—saw decreases in employment within the industry last year, according to the report.
San Francisco ranks second in the latest edition of GEN’s nationally-quoted A-List of Top 10 U.S. Biopharma Clusters, unchanged from a year ago, while San Diego slid one position to sixth, and LA/Orange County slipped one notch to eighth.
“Continued biotech winter”
“California, like the other states in the country, are still showing the effects of the pandemic and the recovery from that, because it was such a large run up of investment and hiring and building of new space, followed by a pretty significant drop off in 2022, 23,” Tim Scott BIOCOM California’s president and CEO, explained in an interview with GEN conducted at the organization’s booth within the convention’s exhibition floor.
“And then we have the continued biotech winter that’s been caused mostly through the instability at the federal level in terms of policy,” Scott added.
He cited NIH funding cuts, the delay in re-authorizing the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) seed funding programs, tariffs, and the “most favorite nation” drug pricing framework championed by the Trump administration as a vehicle for lowering drug prices: “All of these things have led the industry and the investors in the industry to pause.”
Most of the life-sci job decline was concentrated in the Bay Area and San Diego regions, which together accounted for 88% of job losses.
The San Francisco Bay Area saw its life-sci workforce slide 2.7% from 2024 to 137,779 jobs last year, driven mainly by decreasing employment in scientific/research tools, biotechnology, and biopharmaceuticals. The San Diego region finished 2025 with 61,866 jobs, a 2.55% decline from the previous year, due primarily to the loss of jobs in the R&D in physical, engineering, and life sciences and electromedical and electrotherapeutic apparatus manufacturing sectors.
Greater Los Angeles, which BIOCOM California defines as Los Angeles, San Bernardino, and Ventura counties, saw its employment base shrink 0.5% year-over-year, to 143,153 last year, with the largest employment decrease coming in drug wholesaler positions. Orange County’s life-sci workforce also dipped by 0.5%, sliding to 57,213 jobs, driven by cuts in scientific/research tools and medical devices and equipment employment—though Orange County also saw increases in biotechnology and research and testing jobs.
“Significant driver”
“In spite of the slight decrease in growth this year, we’re still at about $400 billion in economic output for California in the life sciences. That’s the second largest industry in California,” Scott said. “It’s still a significant driver of economic activity and of innovation.”
Another driver of innovation, NIH funding, stayed flat last year compared to 2024 at $5.23 billion for all of California. But the number of NIH awards statewide fell 8.5% from 9,384 in 2024 to 8,587 in 2025.
Life science manufacturing jobs fell by 2.1% last year to 143,572 jobs, though they still accounted for more than one-third (35.3%) of all of the industry jobs in the state. Across 31 life science industry sub-sectors, 23 recorded job losses, with the largest declines in medical laboratories and R&D within the physical, engineering, and life sciences job category.
But the state’s life-sci manufacturing segment is eventually expected to grow as drug developers either strive to meet growing demand, reshore their production in the United States to avoid tariffs, or both. Gilead Sciences began construction in September 2025 of a new 180,000 square-foot development and manufacturing facility, part of a companywide $32 billion U.S. investment strategy. Two months later, Novartis opened a 10,000-square-foot radioligand therapy (RLT) manufacturing facility for cancer treatments in Carlsbad, CA, the pharma giant’s third U.S.-based RLT site.
While biopharmas and contract manufacturers have announced hundreds of billions of dollars in new projects, projects announced for California remain mostly under construction, so hiring levels have not yet risen to account for the new manufacturing activity, Scott said.
Potential challenges loom
Two more potential challenges loom for California life science companies—one from Washington, the other from Sacramento.
Scott said BIOCOM California is paying attention to federal efforts aimed at further scrutinizing activity between U.S. and Chinese biopharmas.
Earlier this month, Reps. John Moolenaar (R-MI), chairman of the Select Committee on China, and Congresswoman Debbie Dingell (D-MI), introduced the Biotech Investment National Security Act (BINSA). BINSA would amend the Comprehensive Outbound Investment National Security (COINS) Act, enacted last year, by adding pharmaceutical and biological product development to the list of sectors subject to screening of investments by the U.S. government.
The measure would subject U.S. pharmaceutical licensing deals, joint ventures, and equity investments with Chinese covered foreign persons to U.S. Treasury Department review, as well as explicitly cover licensing deals involving technology and intellectual property. BINSA also requires the Secretary of War (formerly Defense) to assess within 60 days whether U.S. capital investment in Chinese biotechnology negatively affects national security and military readiness.
“We’re trying to find the balance between protecting American interests with regard to intellectual property and also competing with China. And we’re balancing that with cooperating with China,” Scott said. “You can imagine a politician in Washington, D.C., wants to really protect our interests. A biotech entrepreneur in California wants to go anywhere in the world to find resources to be able to move their drug toward the clinic.”
In Sacramento, Gov. Gavin Newsom, who leaves office at year’s end when his second term expires, has proposed permanently limiting the amount of business tax credits that a corporation can claim each year. Starting in 2027, corporate taxpayers would be allowed to claim a maximum of either $5 million or 50% of their pre-credit tax liability, whichever is greater. The limit would not affect taxpayers with less than $5 million in credits.
According to California’s Legislative Analyst’s Office (LAO), recent tax collection data shows that fewer than 100 corporate taxpayers in California would be affected. LAO has estimated that the proposal would raise $850 million in 2026–27, since the cap would only apply to part of the fiscal year, and $1.7 billion to $1.8 billion annually between 2027–28 and 2029–30.
However, the R&D credit likely accounts for most of the proposal’s fiscal effect, according to the LAO, since the R&D credit accounts for the overwhelming majority of business credit usage and carry-forward balances. And the roughly 100 affected businesses include many of the largest biopharma giants, Scott said.
“That is a really big tool for engaging pharma and encouraging investment in California. Without the R&D tax credit, companies are less likely to want to invest in California,” Scott asserted. “The R&D tax credit has had a direct effect on driving the growth of the biotech industry in California.”
The post California Still Golden Despite Job Losses: Industry Group appeared first on GEN – Genetic Engineering and Biotechnology News.
Effectiveness of Neuroplasticity-Targeted Supplements on Neuroinflammatory Markers, ADHD Symptom Severity, and Clinical Scores in Children
Interventions: Dietary Supplement: Inulin; Dietary Supplement: Probiotic; Dietary Supplement: Omega-3 Fatty Acids; Dietary Supplement: Thiamine; Other: Placebo
Sponsors: Khyber Medical University Peshawar; Khyber Teaching Hospital
Recruiting
A man of many words
Brian Sietsema has a favorite word.
It’s somewhat surprising that he can choose just one. He’s the person spellers rely on to confirm pronunciations and answer questions about the roots of the words they’re given at the Scripps National Spelling Bee—arguably the world’s most prestigious competition of its kind. The story of how the word earned the top spot on his personal list may well mark the beginning of his unique career path as both a linguist and a Greek Orthodox priest.
In third grade, Sietsema ventured to a garage sale at a friend’s house with 50 cents in his pocket and picked out three books that struck his fancy. Although they were priced at 50 cents each, his friend’s mother said the books he’d chosen were on special and sent him home with all three, including a collection of Edgar Allan Poe stories called Masterpieces of Mystery. Knowing it contained macabre tales like “The Tell-Tale Heart,” his own mother told him he’d need to wait a few years before reading it. Naturally, he started it right away.
As he read “The Unparalleled Adventure of One Hans Pfaall,” Sietsema was baffled by the main character’s description of arriving at the moon in a balloon. Pfaall reported tumbling into a crowd of people who were “eyeing me and my balloon askant, with their arms set a-kimbo.” Sietsema had never encountered the word akimbo (with or without a hyphen) and asked his parents what it meant. They didn’t know, and it wasn’t in the family’s dictionary. The question also stumped his teachers, and the dictionaries in his classroom and the school library were no help either. “For years, I didn’t know what this word meant,” Sietsema says. It stuck in his mind that there was a word out there that he, his parents, and his teachers didn’t know. He thinks it wasn’t till he got to college that he finally found a dictionary with the answer: The moon dwellers in Poe’s story had been standing with their hands on their hips, elbows turned outward.
“I credit that puzzle with getting me into dictionaries and being curious about etymology,” he says. It kindled a fascination with words—and an abundance of curiosity—that would shape his life’s trajectory and work.
Growing up in Grand Rapids, Michigan, Sietsema attended a Dutch Reformed Christian school and recalls taking part in only one spelling bee, in second grade. It was in the 1970s, when everyone was hooked on phonics—so he overthought the sounding-it-out implications when asked to spell of. “I spelled it U-V, and of course, I was wrong,” he says.
At the time, he thought he probably wanted to work in the church—when he painted himself as an adult for a class project, he dressed his grown-up self in a cassock. But after taking a class in nuclear chemistry at the local junior college in high school, he decided his backup plan was to become a nuclear engineer. So when he went to the University of Michigan, he enrolled in the school of engineering. While he did well and liked his courses, though, he soon realized he felt called to a career in the church after all.

Switching to the college of literature, science, and the arts, he chose the studies in religion major, taking advantage of the interdisciplinary freedom it offered to take classes in literature, art, and more. He also tucked in courses that would fulfill seminary prerequisites such as knowledge of the biblical languages, studying ancient Hebrew and ancient Greek as well as modern languages that might come in handy for theological scholarship (Dutch, Swedish, and modern Hebrew).
Being in Ann Arbor gave Sietsema “a different understanding of the wideness of the Christian world,” as he puts it, and he gradually became less sure about which church he wanted to work in. As he neared the end of his fourth year at Michigan, he still needed a few more pre-seminary courses—and it dawned on him that he’d taken an “awful lot” of languages and thoroughly enjoyed them. So he stayed on for a fifth year to study linguistics as well as German, ancient Aramaic, and modern Arabic. One of his professors encouraged him to go to grad school and insisted that he apply to MIT, which was considered the top linguistics program in the country. To his surprise, he got in.
Sietsema calls his four years at MIT a great adventure: “If I could relive them, I would empty out my bank accounts to do so.”
At MIT he worked with Morris Halle, one of the leaders in generative grammar, which Sietsema describes as a working model of the “chemistry” of language—the parts and processes that form the building blocks of verbal communication. Halle and others had developed counting procedures (akin to measured time in music) that help explain stress patterns (that is, which syllables might receive emphasis by varying such things as stress or pitch). Building on that work, Sietsema’s dissertation proposed that the division of words and phrases into metrical units similar to musical measures can be used to predict where high and low tones fall, which he demonstrated in the tonal patterns of four Bantu languages spoken in Tanzania. At the time, research in this area was seen to have implications for creating natural-sounding machine-
generated speech.
Sietsema calls Halle “a wonderful mentor,” and the two played well off one another. As he was sweltering in his Central Square apartment while printing the final version of his dissertation, Halle called and asked him to stop by. Knowing that Sietsema read Hebrew, Halle, a Latvian-born Jew who’d learned English as his sixth language, wanted to show him a syllable-counting analysis of the 23rd Psalm he’d just completed; Sietsema answered with his own structural analysis of Psalm 90. “I could tell he was delighted to have this young Gentile boy from Grand Rapids, Michigan, who had the same fascination for biblical Hebrew as he did,” Sietsema says.
Today, he calls his four horizon-expanding years at MIT a great adventure: “If I could relive them, I would empty out my bank accounts to do so.” Beyond embracing the intellectual stimulation of the Institute, he took advantage of Cambridge’s many cultural opportunities and cross-registered at Harvard to study French and Ugaritic. All told, he says, he’s now studied about a dozen languages, including the Latin he took in high school and the modern Greek he would add to his repertoire several years after earning his doctorate. (“I always feel like I’m leaving one out,” he says.)
When Sietsema graduated from MIT in 1989, the job market for linguists was “not great.” As fate would have it, though, Matt Alexander, PhD ’92, his best friend at MIT, had already been hired at the University of Michigan, where a one-year position as a visiting assistant professor of phonology opened up that spring. Alexander recommended Sietsema, who handed in his dissertation and got the job, earning an award for excellence in teaching based on student reviews in his first semester.
Shortly after his one-year gig at Michigan ended, he returned to Massachusetts and landed a job as pronunciation editor at Merriam-Webster in Springfield. Although the work was very different from the theoretical linguistics he’d focused on in grad school, “as the guy who had studied a whole bunch of language back in undergrad, it was kind of coming home to old-school philology,” he says. His main job was to ensure that pronunciations—which can change—were up to date. Fluoride, for example, shifted from floo-o-ride in the early 1900s to flor-ide in the second half of the century.
At Merriam-Webster, he made the call on which pronunciations would go into the 10th edition of Merriam-Webster’s Collegiate Dictionary—and in what order of preference. The dictionary, he explains, takes a descriptivist approach that reflects common word usage, so he kept a radio and a TV on in the background as he worked. He’d listen for interesting pronunciations and record them on index cards, noting how each such word was said, who said it, where the person was from, and what the context was. These went into Merriam-Webster’s “huge files” of index cards containing citations of words in actual usage.
Sietsema also had a hand in identifying new words and usages that appeared in the 10th edition, which was initially released in 1993—and he was responsible for the inclusion of definitions for interjectional uses of like. He recognized three informal uses: to introduce a quotation (“So she was like, ‘Let’s go eat’”); to give an approximation (“There were like 10 people in line”); and to emphasize (“He was, like, gorgeous”) or convey something apologetically or vaguely (“I need to, like, borrow some money”). While not a fan of such usages, he recognized them as real linguistic phenomena that had earned a place in the dictionary.
During his tenure as pronunciation editor, he introduced the use of the International Phonetic Alphabet (a standard phonetic notation for all languages) into Merriam-Webster publications long before it became widely used in American mass-market dictionaries. He also oversaw the recording of pronunciations for digital versions of the dictionary and flew out to a San Diego recording studio to supervise the voice actors. When the actors refused to record certain words that offended them, Sietsema had to step into the breach and do it himself. If you go to www.merriam-webster.com and search for a choice two-part expletive the actor Samuel L. Jackson is famous for delivering, it will be his voice that you hear when you click on the icon of the speaker—offering a decidedly less memorable rendition.
Working at Merriam-Webster gave Sietsema access to what he describes as its “fantastic library of old books on every subject imaginable.” He seized the opportunity to delve into historical questions about the development of Christianity—something he’d been curious about. It struck him that Orthodox Christianity was the most original form of the faith that was still around. Having met Katherine Chapekis, a young linguist raised in the Greek Orthodox tradition, during his year teaching in Ann Arbor also nudged him in the direction of Orthodoxy. In 1991, he converted and they married, and she began working at Merriam-Webster the following year as a definer and researcher who tracked down first usages of English words.

At the Greek Orthodox church in Springfield, Sietsema’s facility for languages proved useful when he served as a volunteer chanter, helping the priest lead services in Greek. “I do a good job with the liturgical Greek because I have the phonological knowledge to know how to make my mouth do the things that it needs to do to sound like authentic Greek speech as opposed to an American just rattling off Greek letters,” he says.
He began taking evening classes in Byzantine chant, and before long the bishop was encouraging him to attend seminary. Merriam-Webster allowed him to work four 10-hour days so he could commute to Brookline to study at the Holy Cross Greek Orthodox School of Theology. And after four years, he earned a master of divinity degree.
Sietsema fully intended to go back to being a lexicographer, perhaps eventually getting ordained so he could serve as a substitute priest on weekends. But he’d made what he jokingly calls “a terrible mistake” at the seminary: He’d embraced his studies so enthusiastically that he became the valedictorian and had to give the commencement speech. The archbishop of America—the head of the Greek Orthodox church in the US—came up from New York to attend the ceremony, and he happened to be in need of a deacon who could also serve as a speechwriter. “A few weeks later, I got a call from the archdiocese saying ‘We want you to be ordained, and we want you to come to New York, and we want you to write for the archbishop,’” Sietsema recalls.
In short order, he and his wife moved to the Upper East Side of Manhattan so he could begin his new post as Father Mark (he used his middle name because Orthodox priests must be ordained with a saint’s name, and there are no Orthodox Saint Brians). As deacon to the archbishop and then to his successor, he wrote their speeches and encyclicals on top of many other duties—including chauffeuring them through New York City traffic—and traveled with them around the country and to Greece, meeting President Clinton, ambassadors, members of Congress, Elie Wiesel, and South Africa’s Anglican Archbishop Desmond Tutu along the way. But after two years, as the father of a newborn, he was eager to move on from a job that required putting in as many as 14 hours six or seven days a week. So in 2000, he returned to Michigan to become pastor of the Holy Trinity Greek Orthodox Church in Lansing.
“The World Series can be a four-game sweep and the Super Bowl can be a blowout, but the National Spelling Bee always comes down to one last word.”
Not long after settling into parish life, Sietsema got an unexpected call from the Scripps Spelling Bee. His wife had served on the event’s word panel from 1997 to 2000, and he had traveled with her to one of the members’ off-site gatherings in 1998. He’d tagged along to dinner one night, and they were pleased to meet the person who was responsible for pronunciations in the bee’s official dictionary. But now, just a few weeks before the 2003 event, there was a crisis: The longtime pronouncer had suddenly died. The veteran associate pronouncer would step into his role and take on the job of giving spellers their words, but a new associate pronouncer would be needed to answer spellers’ questions about word roots, monitor pronunciations, and be prepared to serve as the pronouncer if needed. Could he do it? Honored to be asked, Sietsema got the okay from his bishop and said yes.
Little did he know it would become a permanent gig. After 15 years of answering root-word queries, when the bee expanded in 2018 he began serving as a pronouncer for some of the earlier rounds as well—though never for the finals. Now he’s the head of a team of associate pronouncers. “It’s just wonderful to see these young people blossom right in front of you, asking their questions and analyzing the word on the spot and figuring out how it all goes together,” he says. He dismisses the idea that the kids have photographic memories, saying they’re “really just good little word detectives.”
As a member of the bee’s word panel, Sietsema attends multiple daylong meetings to create and fine-tune each year’s list by mining the 500,000 or so words in Merriam-Webster’s unabridged dictionary. “For an introductory round, you want something that’s an interesting word, a useful word, but something that’s gettable,” he says. “For the later rounds, you really want to find something that’s going to challenge the speller. And it’s nice to have a word that’s analyzable.” “Rooty” words—those with obvious roots—are ideal.
The advent of unabridged online dictionaries has streamlined how students prepare for the bee, which once required wading through the dictionary manually to compile word lists. Today, it’s easy to generate lists of words derived from a particular language to study their roots, for example. Meanwhile, the competition has become increasingly fierce, and once-verboten terms like geographical names are considered fair game. For some of the words in the hardest rounds, “it looks like you’re just taking a spoonful of alphabet soup,” he says. “And that’s for the spellers who really, really are committed to learning just about every word they can in the dictionary.”
When it gets down to the last spellers in the final round, there’s an electric feeling in the room. “It’s always a close competition,” he says. “The World Series can be a four-game sweep and the Super Bowl can be a blowout, but the National Spelling Bee always comes down to one last word, and that’s what makes it exciting each and every time.”
The philosopher Friedrich Nietzsche famously wrote that a characteristic of theologians is their “unfitness for philology,” meaning they can’t be trusted to interpret texts with objective accuracy. He also maintained that a sense of restraint characterizes a good linguist. Sietsema says he’s right on both counts. When linguists analyze texts, “we know what we don’t know, and that’s important because you don’t find meaning where it’s not in the original,” he says. He thinks the well-trained linguist has a mission to the world of theology: to help clarify what is an appropriate interpretation of a sacred text and what is going too far.
He’s put his unique blend of skills into practice. In the early days of the covid pandemic, for instance, a Greek Orthodox scholar defended the practice of continuing to use a single spoon to administer communion. The scholar argued that holy things cannot cause harm and that abandoning them for fear of an earthly disease was far more dangerous than the disease itself, citing a passage from a homily of an archbishop of Constantinople in the fourth century CE saying “nothing is worse than to relegate spiritual things to human reasoning.” Sietsema responded with a thoughtful defense of reason, pointing out that the scholar’s argument relied on a mistranslation of logismoi, which he explained refers not to the faculty of reason but to negative mental habits, such as flawed reckonings, intrusive thoughts, or vain rationalizations. He countered that the church very much values reason and advocated “the exercise of good sense, good science, and compassion,” arguing that “those who pit faith against the faculty of reason end up losing one or the other or both.”
Sietsema’s time at MIT, he says, taught him to pay attention not only to what’s in data sets but also to what’s not there that could be. “That particular muscle gets used in both linguistic analysis and lexicography, as well as in pastoral care,” he says. “When you’re listening to people pour out their hearts, it’s important to notice what they’re saying and what they’re not saying.”

As both a priest and a linguist, he’s called on to notice and remember. Attention to detail matters whether he’s gearing up for the celebration of Pascha, or Easter, at Holy Trinity or preparing for the National Spelling Bee, which he calls “the holy week of spelling.”
This spring, before heading to Washington for his 24th National Spelling Bee in May, Sietsema reflected on what words he might add to his list of favorites. A top candidate was one given to Evelyn Blacklock, a speller in his first bee as associate pronouncer in 2003: clepsydra, meaning an old-style water clock. “She didn’t know it, but through a series of questions to me about the Greek roots of the word—from kleptein (to steal) and hydōr (water)—she was able to divine the English spelling,” he recalls. “It was so satisfying to watch this feat of word sleuthing happen in real time, and it gave me a good insight into the importance of my role at the bee.”
It seems unlikely, however, that akimbo will ever lose top billing on his list. It’s easy to imagine Sietsema facing the future with his own hands on hips, elbows out, embracing linguistics, theology, and scientific reason as he shares his joy for life and the words we use to describe it.
Solid Tumor CAR-T Therapy Approved in China, a World First
In a landmark advance for cellular immunotherapy, CARsgen Therapeutics has received regulatory approval in China for satricabtagene autoleucel (satri-cel; CT041), the first CAR-T cell therapy globally approved for the treatment of a solid tumor.
The National Medical Products Administration (NMPA) of China approved satri-cel for Claudin18.2 (CLDN18.2)-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma (G/GEJA) patients who have progressed after two prior lines of therapy. The decision is a turning point for the CAR-T field, which has improved hematologic malignancies but has struggled to overcome solid tumor biological barriers.
The approval addresses a major unmet need in gastric cancer, the fifth most commonly diagnosed cancer and the fifth leading cause of cancer-related death worldwide, with more than one million new cases and over 750,000 deaths annually. East Asia, particularly China, accounts for 40% of global cases due to risk factors like Helicobacter pylori infection, dietary exposures, and an aging population.
Despite advances in chemotherapy, targeted therapy, and immune checkpoint inhibitors, advanced gastric cancer patients have poor outcomes, especially after multiple treatment lines fail. CAR-T therapy first entered clinical testing for solid tumors in the late 1990s and early 2000s, with pioneering studies targeting ovarian cancer and later neuroblastoma and colorectal cancer, laying the groundwork for today’s next-generation cell therapies.
Satri-cel is an autologous CAR-T therapy that targets CLDN18.2, a stomach-specific tight-junction protein that is highly expressed in gastric and pancreatic cancers but has limited expression in normal tissues. The therapy uses a humanized anti-CLDN18.2 CAR construct that is linked to CD28 and CD3ζ signaling domains, which allows for targeted elimination of tumor cells.
The program’s CARsgen preconditioning strategy boosts CAR-T activity in the immunosuppressive solid tumor microenvironment. Patients receive low-dose nab-paclitaxel to increase CAR-T cell infiltration and antitumor efficacy in addition to cyclophosphamide and fludarabine lymphodepletion.
Clinical evidence supporting approval comes from a randomized confirmatory study published in The Lancet in 2025. In heavily pretreated patients with advanced G/GEJA, satri-cel demonstrated clinically meaningful efficacy and a manageable safety profile compared with available treatment options. The results provide one of the strongest demonstrations to date that CAR-T therapy can generate meaningful clinical benefit in solid tumors.
Importantly, CARsgen is already aggressively pursuing a development strategy beyond late-line gastric cancer. Currently, there are Phase Ib studies in advanced gastric, gastroesophageal junction, and pancreatic cancers, a confirmatory Phase II study in advanced G/GEJA, a Phase Ib study evaluating satri-cel as adjuvant therapy in pancreatic cancer, and investigator-initiated studies evaluating adjuvant and first-line sequential therapy. Satri-cel is being tested in a Phase Ib/II trial for advanced gastric and pancreatic adenocarcinoma outside China, demonstrating its global development goals.
The program has also been the subject of considerable regulatory attention. The FDA has designated satri-cel for CLDN18.2-positive gastric and gastroesophageal junction cancers as an RMAT and Orphan Drug. In Europe, the therapy has been awarded Orphan Medicinal Product designation and PRIME status by the European Medicines Agency. In China, the NMPA designated this product a Breakthrough Therapy for advanced gastric or gastroesophageal junction cancer patients who had failed at least two lines of treatment.
Satri-cel may be the first CAR-T therapy to clear the regulatory finish line in solid tumors, but the competition is heating up. Several companies are developing CLDN18.2-targeted CAR-T, T-cell engager, and antibody programs. AstraZeneca’s zolbetuximab franchise validated CLDN18.2 as a gastric cancer therapeutic target, and Chinese and U.S. biotech companies are developing cell therapy programs to replicate or improve on satri-cel’s results.
For cancer specialists and cell therapy specialists, satri-cel’s approval is not just a new treatment option but a proof-of-concept that engineered cellular therapies can successfully address the challenges of solid tumors. Whether this breakthrough can be applied to other tumor types remains to be seen, but the field has crossed a milestone that has eluded oncology for decades.
The post Solid Tumor CAR-T Therapy Approved in China, a World First appeared first on Inside Precision Medicine.
Evaluation of Benign Joint Hypermobility and Serum Prolidase Levels in Children Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Compared to Healthy Controls
Sponsors: Antalya Training and Research Hospital
Completed
Functional Outcome Prediction in Young Adults With Mental Health Symptoms Using Machine Learning and Large Language Models: Longitudinal Observational Study
Paradoxical reflex bradycardia in paroxysmal sympathetic hyperactivity following traumatic brain injury: a case report
Inside the world’s deepest and longest subsea road tunnel
It’s cold, it’s very, very noisy, and—if I can be quite honest with you—I’m not feeling super relaxed.
I’m currently around 300 meters, or 1,000 feet, beneath the North Sea, in a dark, dank cave. It smells weird. And I am increasingly aware of the pressure from millions of tons of seawater just above my head, pushing down with a force of more than 500 pounds per square inch. Picture a baby rhino standing on a postage stamp.
Only fabulous engineering is keeping me from being crushed, drowned, disappeared. My safety goggles are foggy.
Just a few hundred meters away, someone is about to blow up a giant rock wall. Luckily, earlier that day I was given a full safety briefing, and I’ve got a special hard hat on. “Don’t worry—if you don’t make it, we’ll have your stuff sent back to your office,” geologist Anne-Merete Gilje tells me, straight-faced. Ah, Norwegian humor.
“It’s kind of a lifestyle. You have to be a little bit crazy to work underground all the time.”
Niclas Brusehed, tunnel foreman, Implenia
I’m in this odd situation under the iconic fjords of Norway to visit what will soon become the world’s longest and deepest subsea road tunnel, called Rogfast (short for “Rogaland Fixed Link”). I want to understand how you make something as audacious as a 26.7-kilometer (16.6-mile) highway that sits 390 meters (1,280 feet) below the sea at its deepest point. And also—at a time when it can feel hard to get anything done, especially in the US—to reassure myself that ambitious engineering is still possible. That we can still make things.
The Norwegians already have the world’s longest subsea tunnel, the 14.4-kilometer Ryfylke, though Rogfast will dwarf it. Their expertise has attracted attention from Japan, Spain, Morocco, and even a number of US states, whose representatives were due to visit the site in May, just weeks after I went. They, too, want to know how Norway does it.
The answer: tons of explosives.
The entire endeavor feels like an obstinate refusal to give in to physics and geology. “It’s always exciting,” Niclas Brusehed, a tunnel foreman at Implenia, a Swiss firm involved in the project, tells me. “Every blast creates a new world.” There’s not just the blasting of the tunnel itself—although that is an epic project on its own—but an immense logistics challenge involving huge ventilation shafts, extreme pressure, underground roundabouts, and the complex Norwegian geology. Oh, and the water. So much water.
“This is the longest continuous blast on the sea,” says John Olaf Østerhus, assistant project manager at Implenia. “Never been done before. We can’t buy a book to see how we do this.”
All right, time to fish my phone out of my safety suit—don’t want to forget this.
On another planet
Arriving at the rock face where the tunnel hits seabed feels like being on the moon. It’s a huge slab of stone at the end of a long, dark, wet, wide passageway that’s lit (barely) by electric lights. Giant vehicles carting tons of rocks rumble past periodically, and we pull to the side of the road to let them by.

Workers clock in for 12-hour shifts, 6 a.m. until 6 p.m., deep in the bowels of the Earth where no natural light can reach. Twelve days on, 16 days off. They eat their lunch at a table in this damp cave surrounded by portacabins plastered with safety notices. “It’s kind of a lifestyle,” says Brusehed, laughing. “You have to be a little bit crazy to work underground all the time.”
These crazy engineers are here to make tunnels the Norwegian way. The nation frequently uses what’s known as the drill-and-blast method instead of the tunnel-boring machines that are more typical elsewhere. This approach offers more flexibility for long, complex operations with varied rock types. Each blast adds about five to six meters to the tunnel.
Rogfast is being built inward from the ends to speed things up. The construction company Skanska is leading from the north, coming from the island of Vestre Bokn; Implenia has joined a company called Stangeland to tunnel from Randaberg in the south, which is where I am. Both teams use multiple laser scans each day to consistently measure their orientation and check that the tunnel is exactly where it should be. The two ends should meet sometime in 2029, with no more than just a few centimeters of deviation.

Norway has constructed more than a thousand kilometers of tunnels over the past several decades. The depth and length of these make the best efforts to date of Elon Musk’s Boring Company—a mere 2.7-kilometer tunnel in Las Vegas that is just 3.6 meters wide—look rather pathetic. The country’s spectacular setting makes such builds necessary; while Norwegians are proud of having the second-longest coastline in the world after Canada, getting up and down the west coast requires multiple ferry rides between islands, which can move extra slowly when the weather’s bad.
After it’s completed, which is scheduled to happen in 2033, Rogfast should help eliminate two ferry routes and cut the five-hour journey between the southwestern cities of Stavanger and Bergen by 40 minutes. It will funnel four lanes of traffic deep beneath the fjords of Boknafjord and Kvitsøyfjord, and at one section a relatively scant 50 meters of rock will separate the drivers speeding through the tunnel from the bottom of the North Sea. There are also, delightfully, two undersea roundabouts located 220 meters below sea level.
But the first job is to contend with all that water.
The never-ending battle
Subsea tunneling is defined by a constant, ultimately unwinnable battle with the ocean. The sheer weight of the sea above you, and the crushing pressure, means the water will always find a way in. “It’s the volume and the pressure that’s the biggest risk,” says Ole Magne Rønning, project leader for Implenia/Stangeland.
So before tunnel engineers blow stuff up, they need to check for leaks. Into the rock face ahead of them, they drill a number of narrow holes that go 25 to 30 meters deep to see how much water comes through. Even a small probe can unleash a torrent within seconds, says Rønning. When road traffic eventually rumbles through these tubes, water will still trickle from the rocks; it will be redirected into mini reservoirs dotted throughout the tunnel network before being pumped back out.
Since stopping the water entirely is impossible, the game is instead to push it away as best you can. If the leakage in front of the rock face exceeds a certain limit—around four liters per hole per minute—then the next stage is “grouting”: pumping a mixture of cement-like sludge into new holes that fan out in the ceiling above and around the face. Ideally, you address the leaks that are ahead of you; “it’s a lot more difficult to stop a leak that’s behind you,” says Rønning.
At one point deep below the sea, I chat with Tarald Johan Nomeland, the project’s grouting specialist. He’s big and bearded, perhaps one of the most Norwegian-looking men I’ve ever met. He stands, towering above me, and shakes my hand in his giant bear-like paw. Grouting is in Nomeland’s family; his dad did it too. He loves it. “There’s not necessarily just one solution to a problem,” he says, eyes flashing with delight as he describes fighting the interminable battle with the water. “There may be many solutions.”
The amount of grouting needed determines how fast the project can move. On the Skanska side, for example, some weeks the face moves 30 meters; others, as few as 10.
This isn’t made any easier by the rock itself. The seabed around Norway was shaped by glaciers during the Ice Age. As the ice retreated, it dragged softer rock with it, carving out the fjords for which the nation is so famous. But this legacy makes digging subsea tunnels particularly gnarly. Much of what’s left is the hard, difficult-to-break stuff.
And it’s not just one type of rock, either. There are “big wide areas where we don’t know what’s down there,” says Gilje, the geologist who is a project manager for the Norwegian Public Roads Administration, which is in charge of the entire project. Before any construction started, boats took core samples from the seabed along the planned tunnel route. Seismic surveys from the ocean surface—like those that look for oil in the region—helped fill in the gaps.
Each kind of rock presents its own challenges, so the engineers “have different techniques for different problems,” Gilje explains. For example, they found that one southern section contains a lot of phyllite. Phyllite is considered “nice” to work with. It is formed from a combination of shale, siltstone, and mud over time and is pretty compact, with few cracks to let water through. Its compact nature means it requires more explosives per blast, however. It also contains a lot of quartz, which is toxic when released into the air during blasting. So workers wear monitors to measure their exposure, and a curtain of water sprayed in front of the rock face helps prevent too much from drifting into the tunnel.
The northernmost part of the route, meanwhile, is made mostly of solid granite and a similar rock called gneiss. Both are hard but contain fractures that allow the seawater to trickle through.
The rock type can also change over just a short distance. So during the dig, every 80 meters or so, an engineer sends sound waves through the face to expose its secrets and help evaluate its structural integrity. The rock is graded on a scale of 1 to 5, with 5 being the worst and least stable. “When you are reaching class 5, then it’s almost like soil. It’s not rock anymore,” says Rønning.
This investigation informs the kinds of structural supports each section will need—from steel rods that fan out above the rock face like an umbrella, for the strongest rock, to reinforced-concrete arches that hold up the weakest. To seal everything off, the team sprays a substance called “shotcrete,” liquid concrete mixed with reinforced-steel fibers, onto the walls throughout. A plastic membrane and concrete panels are fitted later.
“It’s going to be a very safe tunnel,” Gilje says. “It’s going to last for 100 years.”
Strange dangers
While I may not be brave, at least I don’t get seasick. Back at the surface, I board a small ferry that putters and sloshes its way from the mainland to Kvitsøy, a sparsely populated municipality made up of 365 separate islands and islets—something its 550 or so inhabitants are very proud of, even though most of these islands are uninhabited chunks of rock.
For the next few years, Kvitsøy’s population will experience a tiny boom as its largest island hosts a semipermanent encampment of contractors and engineers working on what is probably the most complex part of the Rogfast project: the giant ventilation shafts that will sit roughly halfway along the tunnel’s length to bring fresh air into the entire network, and remove the stale air in turn.
It’s also one of the reasons why road tunnels are much more complex than rail tunnels. Cars pump out fumes that have to be vented away. During construction, fresh air flows in via huge plastic tubes suspended from the ceiling, but eventually, Rogfast’s air will come in through two nine-meter-wide shafts that will bore down from Kvitsøy’s surface: one to bring it in, one to take it out.

Creating these shafts is a wild process. First, narrow boreholes are drilled from the ground down into the tunnel 210 meters below the surface. A vertical drill rig is then pulled up through the hole from the bottom, widening the shaft to 2.4 meters as it ascends.
Then explosives are set off on the island’s surface, bashing down through the rock to widen the shaft. A large digger pushes the resulting debris down the narrower, not-yet-exploded length of shaft below, sending rocks barreling toward the tunnel at the bottom like socks tumbling down a laundry chute. Trucks haul away the fallen rocks. This process happens in stages, repeating at regular intervals, opening up the passage a bit deeper with each pass. Once it’s all done, steel rods are installed in the shaft’s walls to keep it secure.
Down below, I stand beneath one of the narrow guide holes for one of the two ventilation shafts. The ceiling soars overhead—a strangely beautiful cathedral, cragged and shadowed by lamplight.
Besides poisonous air, the epic nature of these engineering projects throws up other surprising dangers. For example, Rogfast will take about 30 minutes to drive through. It doesn’t seem that long, but the project’s designers worry that the monotonous environment may lull some drivers to sleep.
Engineers faced this problem with Ryfylke—which, as the current longest subsea road tunnel, has been a testing ground for its bigger sibling. It relieves the tedium with a large hall that opens up in the middle of the tunnel, lit by colored lights that change each day. When Rogfast is finished, artists will be invited to do something similar, using lights, colors, and shapes to keep drivers alert.
Then there are the environmental risks. What is there to do with all the loose rock created by the blasts? The engineers predict 8.5 million cubic meters’ worth. That’s enough to fill more than 2,500 Olympic-sized swimming pools. The solution is to bring it back to the surface, where it can be used to create new land. To do this, the project employs a giant barge designed to split open and dump 350 tons of rock in one go.
But adding more rock particles to the water can make it hard for fish to breathe, says Elizabeth Austdal Paulen, Implenia’s environment lead on the project and my fellow passenger on the windy (and soon to be redundant) ferry over to Kvitsøy. Her team monitors their levels in real time: If the particulate count is too high, the drops must pause until the new rock has settled on the seabed. The goal is to protect lobster fishing, a vital part of the local economy, and to safeguard the breeding time for cod, which was an issue when I visited.
Finally, of course, on top of all this are the many hazards for the people who are actually doing all this blasting and digging and hauling. Or, say, for the visitors who are finding their inner nine-year-old getting a little too giddy about what’s next.
Time to blow
Before I’m allowed underground, I must sit through a short safety briefing, where I learn there are multiple hazards when you’re that deep. Fires, for instance, can break out, exacerbated by the way the salt water affects electronics. Just a week earlier, a car caught fire somewhere deep within the network. “You have to be aware all the time,” says Anne Brit Moen, the project lead for Skanska. “It’s a very harsh, harsh climate.”
After the session, I’m given a hi-viz suit, the hard hat (which has built-in ear protectors), gloves, safety glasses, and reinforced boots. I get instructions on how to operate the oxygen mask that will be in the car with me, and a device to put in my pocket that will track my exact location on screens in the control room. The device also acts as a personal warning system: If it vibrates and a blue light appears, then a blast is imminent and I must get to safety; if it vibrates and glows red, umm, well, that’s bad news and it’s time to evacuate.
“If you’re the first to the rescue chamber, press the green button … close the hatch and sit down and be calm.”
Ketil Myklebost, project manager, Implenia
But let’s say I can’t—I’m too deep underground. Then there is a second, less fun option. I’m given instructions on how to access the rescue chambers. These metal boxes—about the size of a large van—can squeeze in around 16 people, and each contains chocolate, water, radio equipment, a defibrillator, and enough oxygen for 24 hours. I see them dotted throughout the tunnels as we drive through. Worst-case scenario, I’m supposed to get to the nearest one, sit tight, and hope to get rescued.
“If you’re the first to the rescue chamber, press the green button for 15 seconds to release pressure,” says Ketil Myklebost, a project manager at Implenia. “And then close the hatch and sit down and be calm.”
Calm, right. Okay.
In the hours before my visit, a huge drilling “jumbo” rig puts as many as 180 holes deep into the rock face. The number, angle, depth, and spacing of the holes is calculated in advance using software but finalized at the face—here, they’re almost six meters deep. At one point, I clamber up into the jumbo and inspect the pattern on its screen, matching it against what I can see on the huge rock face, which stands more than 12 meters tall and wide.
The holes have been stuffed with an explosive slurry. (Someone quips that if I get any on my clothes, I’ll be stopped at the airport as a terrorist. A Norwegian joke, again.) As I watch, workers in a kind of cherry picker fit each hole with a detonator and make sure they’re all connected to one another by wire, ready to be triggered remotely.
Then my personal safety device starts vibrating. When I take it out of my pocket, it’s blinking blue. Showtime.
How far back do I need to be? “It’s dangerous in this direction 500 to 600 meters, but if you’re around the corner you can be closer,” says Sveinung Brude, project manager for the Norwegian Public Roads Administration.

I stand by the worker who will trigger the blast from what looks like a small briefcase with an antenna. Then he presses the button.
The shock wave hits me before I hear it. My chest vibrates. In the first few milliseconds, a propulsive thump briefly stuns my senses, followed immediately by a rolling, crumpled thunder.
Just a moment later—almost instantly, really—wind billows through the cavern. Rocks clatter as they crash off the walls. I try not to show any panic. (That was meant to sound like that, right?) A hush falls, and there’s just the tinkling of stones as they bounce and skip amid the rubble.
Dust rises into the air, and there is a strange smell.
Through my ear protection it sounds like the end of the world.

The explosion itself is a beautiful choreography: Blasts are initiated one after another, starting from the center. In video footage, you can just about hear the sequential pitter-patter of the charges as they go off. (In person, it’s a bit more all-at-once and overwhelming.)
Rogfast has just crept another few meters closer to completion.
I find myself grinning. Maybe there’s something extremely primal about being near an explosion? I’m not sure. I look down at my hand, where I have my phone out, recording the intensity of the moment.
Except … I wasn’t recording. The stupid rubber safety gloves I’m wearing must have stopped the command from going through.
Oh no. Oh no.
A once-in-a-lifetime opportunity, and I, uh, blew it. “I WASN’T RECORDING!” I shriek.
“It’s better that way,” says Rønning, walking off into the gloom. “You’ll remember it.” How very Norwegian.

