Buoyed by the remarkable results of the OPTIMA trial presented at the ASCO Annual Meeting, Veracyte this week announced the U.S. launch of the Prosigna Breast Risk of Recurrence (ROR) test, a genomic test for patients diagnosed with early-stage hormone-receptor positive (HR+) breast cancer.
“Prosigna is the only test proven to be predictive for chemotherapy benefit in a Phase III prospective trial for patients with up to nine positive lymph nodes, including premenopausal women, all of whom were recommended to receive ovarian suppression,” Phillip G. Febbo, MD, chief scientific and medical officer at Veracyte, told Inside Precision Medicine.
The Prosigna test determines a patient’s ROR score and estimates the 10-year probability of distant recurrence. It thus help guide treatment decisions, including predicting whether high risk patients are likely to benefit from chemotherapy or may safely achieve optimal outcomes with endocrine therapy alone, helping clinicians to make personalized care plans for their patients.
Prosigna will be available to order starting June 8, 2026.
“Every patient diagnosed with breast cancer deserves answers they can trust about what their cancer means and what comes next,” said John Leite, PhD, chief commercial officer, Veracyte.
“Prosigna gives patients and their oncologists a deeper understanding of their individual risk of recurrence, and, for many, whether chemotherapy will truly benefit them or whether they can safely avoid it. That kind of personalized insight can bring greater confidence and reassurance as patients navigate decisions that will shape their care and future health.”
In the U.S., more than 225,000 new HR+/HER2- breast cancer cases are diagnosed each year. When breast cancer is diagnosed early and treated appropriately, five-year survival rates reach 92%.
“For decades, clinical staging just comprised tumor size and nodal status together with pathology. This was the standard approach to determining whether patients with HR+/HER2- breast cancer need chemotherapy. Many node-positive patients routinely receive chemotherapy as standard of care,” Febbo said.
He added, “And yet, chemotherapy is likely to only benefit a relatively small fraction of these patients.”
The OPTIMA trial uses the Prosigna test to guide therapy and testing. Those patients with a low Prosigna ROR (<60) can safely avoid chemotherapy. OPTIMA shows that tumor biology, as evaluated by the Prosigna test, provides information beyond traditional clinical factors.
Prosigna is based on the PAM50 genomic classifier, which classifies tumors into four intrinsic subtypes. Prosigna, the company said in a press release, “uniquely combines intrinsic subtypes and proliferation score with clinical pathological factors into a single comprehensive analysis to calculate a patient’s Risk of Recurrence (ROR) score and predict 10-year probability of distant recurrence.”
Veracyte’s portfolio includes multiple cancer types, including tests for prostate cancer (Decipher Prostate), bladder cancer (Decipher Bladder and TrueMRD for muscle invasive bladder cancer monitoring), and others. The company said, “Prosigna’s intrinsic subtyping data positions us well for future expansion. While ROR scoring is specific to HR+/HER2- disease, the underlying intrinsic subtyping information spans all breast cancer types.”
More than 225,000 new HR+/HER2- breast cancer cases are diagnosed annually, with approximately 75,000 patients having node-positive disease annually. The OPTIMA trial demonstrated that more than two-thirds of clinically high-risk patients (68%) can safely avoid chemotherapy—a significant population previously assumed to require treatment based solely on nodal status.
Researchers at the Massachusetts Institute of Technology (MIT) have developed a catheter-based nanosensor that can detect the recurrence of bladder cancer at an earlier stage by identifying a biomarker released by tumors directly within the bladder. The technology, detailed in Nature Nanotechnology, combines carbon nanotube sensors with a rotating optical imaging device to create what researchers describe as a three-dimensional chemical imaging platform capable of locating cancer-associated biomarkers within tissue.
“It’s like a camera for molecules instead of light,” said Michael Strano, PhD, a professor of chemical engineering at MIT and senior author of the study. “If you have a billion nanosensors in an array, you can use them to make a chemical image that helps you locate their source.”
Roughly 85,000 people in the U.S. are diagnosed with bladder cancer each year, and more than half of patients experience recurrence within five years. The disease also carries among the highest lifetime treatment costs because patients require ongoing surveillance.
The new method addresses a major challenge in detecting bladder cancer recurrence, which currently relies on urinalysis to look for signs cancer has returned. Using urine for detection is hindered since biomarkers of cancer recurrence are diluted, degraded, and are often cleared shortly after they are released by the new tumor.
To address this, the MIT researchers targeted the matrix protein 22 (NMP-22), an FDA-approved biomarker for bladder cancer. While it is possible to detect NMP-22 in urine, the shortcomings of that method often mean that the cancer is often only found at a later stage of development.
To overcome this gap, the MIT team looked for a way to develop a sensor that could work inside the bladder. Their device consists of a urinary catheter coated with specialized nanosensors that detect the presence of NMP-22. A miniature rotating ball lens embedded in the catheter tip emits laser light and collects fluorescent signals generated by the nanotubes when they interact with the target biomarker.
Over the past decade, Strano’s laboratory has focused on developing carbon nanotube-based sensors that can identify specific molecules. The team customizes nanotubes for each application by applying different polymer coatings that function as “synthetic antibodies,” enabling them to bind to disease biomarkers. Previous development efforts in the lab have yielded sensors capable of detecting molecules such as hydrogen peroxide, riboflavin, and viral proteins.
For the bladder cancer application, researchers engineered a phospholipid-containing a synthetic polymer that selectively recognizes NMP-22. The project was partly motivated by earlier computational modeling conducted by the team, which suggested that placing sensors near an emerging bladder tumor could produce “a more than 50,000-fold increase in detection limit by minimizing biomarker dilution and degradation.” That finding pointed toward the potential advantages of measuring biomarkers at their source rather than after they enter urine.
In experimental testing, the platform achieved a 182-fold signal enhancement compared with biofluid sampling. The new technology was tested in multiple ways. The researchers first tested the nanosensors against six bladder cancer cell lines and healthy fibroblast cells and found distinct sensor responses associated with cancer-cell apoptosis. The team also used the chemotherapy drug gemcitabine to induce cancer cell death in vitro and monitored the resulting release of biomarkers. siRNA analysis confirmed that NMP-22 was a major contributor to the detected signals.
Researchers then evaluated the platform in porcine bladder models using a catheter coated with the specially designed nanotubes. Using a rotating ball lens system, they generated chemical maps showing the location of biomarker sources and demonstrated detection at distances up to two centimeters from the source. The researchers also reported a simulated tumor resolution of 16 square millimeters.
The chemical imaging capability is a unique attribute of the new method and the information it can provide should be very useful for treating recurrent cancer. “If you are scanning over a region of tissue, you would like to know not just that there is a signal indicating that a tumor is there, but also its location so that you can treat it or perform a biopsy,” Strano said. “Before an early-stage tumor breaks through the urothelium so that it’s visible, it’s under the surface but still emitting chemical signals that can be imaged.”
While the study focused on bladder cancer, the researchers indicated that the underlying platform may have broader applications. By replacing the nanosensors with versions designed to recognize other biomarkers, the system could potentially be adapted for additional cancers or for diseases affecting the cardiovascular or gastrointestinal systems.
“The beauty of polymer chemistry is that if we understand the molecular structures of target biomarkers and the design principles of binding sites, we can develop new sensors tailored to different diseases,” said lead author Wonjun Yim, PhD.
Future work will focus on expanding the range of detectable analytes, developing multiplexed sensor arrays, conducting omics-based biomarker validation studies, and improving optical engineering. The researchers also aim to miniaturize the imaging system and integrate the technology into cystoscopes already used in clinical practice.
Would you take a payment to ramp down your electricity use? Would it change anything if you were doing so to help power a local data center?
Google just signed a new deal to help pay for a virtual power plant (VPP) in the largest power grid in the US. The agreement is with Voltus, a leading VPP and distributed energy resources platform.
Voltus will set up the virtual power plant, grouping together devices like electric vehicles and smart thermostats. It’ll pay customers to participate, and the company will dial back power or use the stored energy during times when the grid is stressed. Google will foot the bill for setting it up, and the extra capacity generated by the project will help run its data centers in the region.
This is one of the most concrete examples so far of a tech giant using a VPP to help meet energy demand for data centers. But there are still some lingering questions about just how far this sort of program can go, and what the limits are.
Last year, it felt as if everyone was talking about data center flexibility. A high-profile study from Duke University found that if data centers agreed to decrease their energy demand for roughly 40 hours per year, a whole bunch of them (about 100 gigawatts’ worth) could come online without making new power plants or transmission equipment necessary.
The underlying reason is that our power grid is designed not for our average energy use, but for the absolute maximum: the brutally hot July evening when everyone is blasting their air conditioners, watching Love Island, and microwaving popcorn. If a data center is willing to refrain from pulling so much power during those high-stress times, the grid can happily support it the rest of the year.
One lingering question here is about incentives: How would you get data centers to agree to this? After all, they might not have a very flexible load, especially now that AI use is more widespread—training a model can easily be delayed or shifted, but customer demand is more immediate. Giving up computing capacity could mean losing revenue.
Regulation is one approach that could work here. One proposal in the US would allow new data centers to come online years sooner if they agree to lower demand when the grid is nearing its max. And a new Texas law requires large users to switch to backup power or curtail their demand in emergency situations.
Another approach is for data center operators to pay for other people to be flexible.
Voltus announced a new program in September that allows data centers to finance flexibility on their local grid. The company calls it “Bring your own capacity.” Google is now the first named customer taking advantage of this program.
In the new agreement, Voltus will pay people who agree to participate in the virtual power plant. The plant will be part of PJM, the grid that covers much of the US East Coast. The company says it will be able to aggregate up to 100 megawatts of distributed energy resources each year. The plant should be operational in 2027, according to Voltus.
This isn’t Google’s first foray into flexibility; the company has agreements with utilities across the US to limit or shift its own energy demand, which can help free up grid capacity. As the company pointed out in a blog post earlier this year, though, there are limits on how flexible a data center can be, and not every facility will be able to ramp down its power demand.
“There is no one solution for expanding grid capacity and we’re continuing to explore all options, including the many avenues for load flexibility,” said Michael Terrell, Google’s global head of advanced energy, in an emailed statement in response to written questions.
Once again, I’m wondering about incentives here. These companies are asking homes and businesses to be flexible. Will they agree?
A recent study in California looked at local people’s willingness to participate in managed electric-vehicle charging. Essentially, the program pays people to give up control of when they charge their EVs. This is another way to help smooth out electricity demand and ease the burden on the grid.
The problem? Not many people signed up. With no economic incentive, only 1% of EV owners enrolled in managed charging. At $40 per month (about 15% of their power bill), only 4.6% did.
This is a different situation and a different region from the one in which Google is working with Voltus. (It’s worth noting that the companies aren’t sharing how much they plan to pay the participants, which will obviously be a big determinant in participation for this kind of project.)
But this study shows that even with money on the table, people may not always jump at the chance to cede control of their electricity demand. And it certainly feels relevant that about 70% of Americans oppose AI data centers in their area, according to recent Gallup polling.
Being flexible sounds like a great idea in theory, and these financed VPPs could provide an immediate route to meeting energy demand. But as we move from idea to implementation, it’ll be interesting to see whether trial runs work as intended.
This article is from The Spark, MIT Technology Review’s weekly climate newsletter. To receive it in your inbox every Wednesday, sign up here.
The global biopharma industry is placing increasing importance on regional support rather than only centralized expertise to help complex programs advance. A key benefit is access to local expertise in or near their time zone.
The localization movement “is part of a global shift [in which] companies are assessing how they balance cost, quality, and risks across regions rather than relying on any single market,” Jessay Devassy, PhD, global R&D director, Ecolab Life Sciences, tells GEN.
Ecolab opened a bioprocessing applications lab in Korea this spring. “Being in Korea allows the exchange of ideas in an iterative fashion…so knowledge moves seamlessly between regions. That’s much easier if you’re in their proximity,” Devassy points out.
This is the company’s first bioprocessing lab in Asia. Situated in Dongtan, Korea, it supports process development studies from early- to commercial-scale, focusing on biologics’ downstream purification.
Korea was a logical choice. “Korea is highly advanced in manufacturing,” Devassy continues. Now it’s evolving from a manufacturing hub to a comprehensive biopharma ecosystem, with active contributions from R&D all the way through clinical development, with home-grown and multinational companies alike.
With its biologics manufacturing history, “I think Korea has become one of the most trusted locations globally,” he says. “Its quality standards are well-aligned with North American and European standards.” Consequently, global clients are assured that the same approaches and standards are applied to development as in the United States or Europe.
Korea’s aspirations
Government support is part of that. The Korean government designated biopharma as a strategic industry after COVID-19 and reiterated that goal in 2023’s Third Five-year Comprehensive Plan for Development and Support for the Bio-Pharmaceutical Industry. Key points include developing two blockbuster drugs by 2027, doubling pharmaceutical exports to $16 billion, and positioning Korea among the top six nations for pharmaceutical development.
At the end of 2025:
New venture capital investments in biotech and medical companies reached $830 million, up approximately 11% from the prior year.
Total venture investments in the biotech and medical sector rose more than 29% from 2024, more than for any other industry.
Continuous bioprocessing is expected to experience a compound annual growth rate of nearly 20% between 2025 and 2030, reaching revenues exceeding $21 million.
Challenges
The competition to attract biopharma companies is robust. India is the fastest-growing Asia-Pacific market, but, Devassy says, “China has a cost advantage…[in] manufacturing and development.” It’s also the largest biopharma market in the Asia-Pacific region.
“Japan has more established domestic systems for biomanufacturing,” Devassy continues. According to Grand View Horizon, Japan leads the pack for projected revenue from continuous bioprocessing to 2030.
Devassy positions Korea “somewhere in between” China and Japan. “It’s strong technically, but is still navigating regulatory complexity and global competition.” Currently, it generates 2.2% of the world’s continuous bioprocessing revenues.
“Biopharma exports from Korea have seen strong growth recently…and Ecolab is playing a strong part in supporting the manufacturers behind that growth,” Devassy says. “This is our first step toward making our global expertise accessible to growing markets in Asia.”
Viral vector production and training schemes designed to foster development of an AI-ready workforce dominate the list of projects selected for support by the U.S. National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL).
The institute, a public-private partnership focused on advancing manufacturing and solving industry challenges, announced its latest funding awards, explaining that the 39 recipients would support U.S. production and talent development.
Sandeep Kedia, NIIMBL senior technology fellow and project call program lead, says the projects “represent the kind of innovation needed to strengthen the nation’s biopharmaceutical manufacturing capabilities.
“By bringing together advanced process analytical technologies, AI-driven optimization, and next-generation production platforms, our members are helping accelerate the adoption of transformative technologies across the industry,” he adds.
Several of the selected projects focus on the production of adeno-associated viral (AAV) vectors—hollow viruses used to deliver genetic information—which play a crucial role in cell and gene therapy manufacturing.
For example, researchers at Michigan Technological University will work with industry partners on an aqueous two-phase continuous vector purification system. The aim is to boost yield while reducing cost, labor, and analytical complexity.
Similarly, a team at North Carolina State aims to develop “improved purification materials that can better capture full AAVs, along with machine-learning software that identifies optimal process conditions.”
The third vector-focused project will see an MIT group work with EMD Millipore, Landmark Bio, and Virica Biotech to try to reduce the number of empty viral capsids inadvertently made during vector production.
The researchers will combine an approach called decoupled replication-initiated vector encapsulation, or DRIVE, with various process control strategies to create a platform that makes high-titer, high-quality rAAVs.
According to the MIT team, “By reducing [the proportion of] empty capsids, the approach can streamline downstream purification, reduce time and cost, and improve the overall quality of gene therapy products.”
AI-ready workforce
In addition to the technology projects, NIIMBL will support several training programs with an emphasis on ensuring the next generation of biopharmaceutical engineers are AI-ready, according to workforce director John Balchunas.
“Our workforce initiatives are designed to meet talent needs head‑on by creating more innovative pathways into biomanufacturing careers,” he says, adding, “These new projects will strengthen partnerships and ensure that learners can gain the skills needed to thrive in a rapidly evolving biopharma industry.”
One such project will see a team at Texas A&M University’s National Center for Therapeutics Manufacturing expand an existing effort called NeuroPipes, which seeks to interest neurodiverse people in careers in biopharma. The aim is to provide technical skills training that prepares neurodivergent adults for careers in drug manufacturing.
Another project will see Wistar Institute researchers set up BioPATH, a national consortium focused on advancing workforce training in biomanufacturing, AI, and automation.
The idea, according to the Wistar team and collaborators at the International Academy of Automation Engineering, is to “bridge the gap between foundational bioprocess and GMP knowledge and the emerging needs of automation, data-driven manufacturing, and digitally enabled quality systems.”
Assistant Professor of Pediatrics, The Perelman School of Medicine University of Pennsylvania Director, Clinical In Vivo Gene Therapy Children’s Hospital of Philadelphia
Panelist
Lindsey A. George, MD
Dr. George is a physician-scientist whose clinical expertise is in disorders of hemostasis and thrombosis with a particular interest in hemophilia and hemophilia gene therapy. Her basic science laboratory studies the molecular basis of coagulation that in diminished or excess functional states leads to disorders of hemostasis and thrombosis, respectively. The current focus of the George lab is to merge mechanistic studies aimed at understanding the regulation of factor VIII cofactor function with translational efforts in hemophilia A gene therapy. Her group is additionally interested in understanding the mechanistic basis of questions that have emerged from current hemophilia gene therapy clinical trials as well as general studies of adeno-associated viral vectors (AAV). Dr. George was previously the lead clinical principal investigator of multiple early phase hemophilia A and B adeno-associated virus-mediated gene addition trials. In addition to her clinical practice and laboratory, she directs the Clinical In Vivo Gene Therapy at the Children’s Hospital of Philadelphia that long-term aims to safely and efficiently advance translational and clinical research for in vivo gene therapy for children with genetic disorders.
Steven Gray, PhD
Professor, Department of Pediatrics Co-Director, Gene Therapy Program Director, Viral Vector Facility University of Texas Southwestern Medical Center
Panelist
Steven Gray, PhD
Dr. Steven Gray is a Professor of Pediatrics at the University of Texas Southwestern Medical Center, where he co-directs the Gene Therapy Program and leads the Viral Vector Facility. An expert in AAV gene therapy vector engineering and nervous system gene delivery, his research has helped advance gene therapies for neurological disorders including Rett syndrome, Tay-Sachs disease, Batten disease, and Giant Axonal Neuropathy. Dr. Gray has authored more than 90 peer-reviewed publications, holds over 20 patents, and has contributed to multiple approved and ongoing clinical trials. His work has earned numerous honors, including the American Society of Gene and Cell Therapy’s Outstanding Young Investigator Award.
Broadcast Date:
Time:
Adeno-associated viruses (AAVs) have emerged as one of the most promising platforms for in vivo gene delivery. Ongoing innovation in vector engineering, delivery, and clinical translation is expanding the therapeutic potential of AAV-based approaches across a range of genetic disorders.
This episode of GEN Live will explore the rapidly evolving field of AAV gene therapy. Leaders from clinical and translational research will discuss current advances and challenges in AAV vector development, delivery, safety, and long-term therapeutic efficacy.
The session will provide a broad overview of the current state of the field and foster discussion to define the next era of gene therapy. We will also take questions from the audience, so please bring your questions on AAVs for our panelists as well.
Arthur Caplan’s reflections on medical ethics draw not only on theory but also on lived experience. As a child hospitalized during the polio era, he watched doctors shield families from harsh truths, promising sick children would “go home” when they clearly would not. That early encounter with paternalism sparked a career questioning who medicine serves, who gets protected, and who gets left behind.
In this episode of Behind the Breakthroughs, Caplan argues that modern bioethics is undergoing a profound transformation. Medicine once viewed disability almost exclusively as a problem to “fix,” often with horrifying consequences. He recalls a time when infants born with conditions like Down syndrome or spina bifida were denied treatment and allowed to die. Today, he warns, the danger is subtler but equally troubling: a culture of genetic testing and parental perfectionism that risks defining human worth by what technology can detect.
Caplan also sees a seismic ethical shift from protection to autonomy. Research ethics once focused on shielding vulnerable people from dangerous experimentation after scandals like Tuskegee and the Willowbrook State School. Now, fueled by post-COVID distrust and libertarian politics, public pressure favors “right to try” medicine and personal choice even when evidence is weak or risks are high.
Yet Caplan draws a sharp line at public health. Vaccines, he argues, are not merely personal decisions but moral obligations rooted in responsibility to others. He warns that an obsession with liberty, detached from community ethics, threatens the foundations of public health itself.
Caplan also looks ahead, discussing what he thinks will define the next ethical frontier, the brain. If we can alter the brain, how much can we change and still remain ourselves?
This interview has been edited for length and clarity.
IPM: How did you become interested in medical ethics?
Caplan: When I was about six, in 1956, I was playing with my parents in their bedroom, rustling around, when they noticed my legs weren’t moving well, and my mother freaked out because she knew that meant maybe polio. It was something that all parents knew about at that time, fearing it was incurable, sometimes fatal, and often disabling.
You didn’t know even what to do to prevent it. People tried to close down swimming pools and not have summer camp, but it wasn’t clear what the route of transmission was. They didn’t understand that it could be in wastewater or fecal material.
Off I went, living in Boston, to Mass General. The experience definitely shaped me in many ways in terms of outlook and career. At the time I didn’t like the fact that the doctors and nurses didn’t tell us the truth. They often said, “Arthur is going to go home,” and Arthur was clearly pretty sick, and he didn’t go home. That’s a long-winded way of explaining the genesis of my interest in medical ethics.
One other thing that was interesting that people forget when a newborn is born with a birth defect when they go into a sort of neonatal peds rotation is if the parents say there’s a birth defect and we don’t want it treated, the doctors do not. That included spina bifida. In fact, it included Down syndrome. Those infants were put in a corner and allowed to die through starvation.
IPM: How is genetic testing changing society’s perception of what constitutes an “acceptable” human being, as well as medicine’s responsibility to treat all humans?
Caplan: The idea that medicine has always had a view that disability is something that you have to treat—I don’t agree with that totally. I would like to see that treated as an open question, not a close one. It’s also clear that aside from medicine’s views of disability, the line shifts technologically; some of the things that are disabling are less so as we get better technology.
At NYU, we do face transplants…but we, interestingly, have not really gotten into limb and hand transplants. The reason is we think that the prosthetic opportunities are so good that there’s no reason to do a procedure and then stay on immunosuppression by transplanting a liver.
Disability is often just seen as something where the cost is literally an economic cost. What’s the burden of the person to take care of them in an institution or to take care of and make accommodations for them? If you have a kneeling bus or a ramp in the library and that sort of stuff, but you don’t get in the economist calculations often enough, just measure what it’s like to have an enjoyable life. Forget about what it costs.
There are many issues around disability that I think the world of genetic testing, even genetic engineering, neglects a little.
Counselors have been taught over the years to be neutral, and we use them frequently, particularly in academic settings. But they’re not neutral. They have a list of conditions that they look for and will counsel you on, and then there’s another broad range of things they don’t say anything about.
That boundary is shifting according to parental expectation. There are plenty of wealthy parents who I think won’t accept anything less than a perfect child. If you tell them their kid has any kind of issue, they may well start over. There are other cultures where you tell them their kid has a club foot or a minor issue, and they’re going to try and cope with it. Culture really shapes how we view. What are we going to diagnose? What are we going to treat in the U.S.?
I fear partly what determines what we’re going to diagnose is what we’ve got to test for, not necessarily whether it’s a bad thing, a good thing, a bearable thing, a cultural thing, whatever. It’s almost like, can I charge for this? Then I’m going to add it to the battery.
IPM: What has been the biggest medical moral shift over your career?
Caplan: Research ethics. When research ethics really got rolling, it was in response not to the Nazi concentration camp experiments, although the idea of informed consent came from those abuses when they were put into the court opinion. The emphasis was on informed consent.
All the way back to the Tuskegee study of the early 70s, people were put in experiments, oftentimes institutionalized Willowbrook demented Jewish chronic disease hospital kids; poorly educated Tuskegee kids in asylums; and the Iowa stuttering experiments, where they tried to figure out if they could teach kids to stutter to understand the genesis of stuttering by stressing them, and all of this culminated in the view that research is too risky and dangerous. People need protection from it.
We had a history of protectionism. It was one of these things where you’d have to be insane or inane to be a research subject. Who would want to do that? Look at what happens. People die and they get mistreated and so forth.
Probably around the time just before COVID, we were seeing a shift. It is part of the shift that is represented by MAGA and MAHA, and that is the rise of a notion of “I want more liberty and I want more ability to make my own choices.”
Today we don’t see people demanding protectionism. What we see is them demanding access. What you’re seeing in policy is more ability to give people the right to try things and more ability to say things to people. It may be very risky, but if you were to do it, we’re going to try and make that possible.
Trump is very proud of his efforts in what’s called the “right to try” space. Many states have enacted laws to try and allow people to do this. You can see special laws here and around the world to give people access to stem cells. The therapy, I think, doesn’t really have much evidence for much of anything except maybe, I don’t know, bone marrow transplants or something. But, but they’re using it for arthritis and down syndrome and autism, and who knows? The justification is “Your choice, your decision.” It’s an interesting shift.
There is a popular push, especially in the U.S., to let people take more risk, to let people take informed risks, and to let them do it. Some of the things we see today. You put them in front of an IRB 25 years ago; there is no way that they happen. Just no way.
IPM: Why have vaccines become so divisive?
Caplan: Vaccines depend upon a moral framework of public health, and public health ethics relies on a duty to your neighbor. It relies on an obligation to the community. It isn’t just about your choice. It isn’t just about freedom. It’s about responsibility. When it comes to vaccination, you have a responsibility to ensure that your neighbor’s newborn, who has no immune system and cannot be infected, or the child who has an immune disease and lacks an immune system or has undergone a transplant, or your grandmother, whose immunity is very weak, does not die from the flu, COVID, or something else.
What bioethics failed to do is articulate public health ethics. That’s what mandates are about—restrictions on liberty. That’s what quarantine is about—restrictions on freedom of movement. If you don’t see a duty to others, you’re not going to go along with any of this.
We have within the MAHA movement a real overemphasis on liberty all the time. The surgeon general of Florida said he was going to do away with all vaccine mandates for kids. That’s a bad ethic for public health. You do it that way, and you’re going to have no problem. You can drive drunk as you want anywhere you want to go and speed all you like.
There are libertarian people who would go for these things. They don’t want any government intrusion. I think it’s wrong. I think Thomas Hobbes would say you’re going to have a life that’s nasty, brutish and short if you don’t have some community ethic around in addition to choice. John Stuart Mill, who was actually a big believer in liberty, said, “Your freedom to swing your arm ends at the tip of my nose.” You can’t harm me by your choices. That’s how I say vaccination is. It’s part of the fact that we’re interconnected, that some things we do will hurt others if we don’t limit them, restrict them, and so on. In emergencies we’d have a giant plague.
Their old argument had always been vaccines aren’t safe. Today it’s about freedom. “I’m not against vaccines,” says RFK Jr. “It’s your choice.” My argument is, “Is that your choice?” If you’re in the middle of an epidemic or a pandemic, it is public health’s duty to get you all vaccinated to make this thing go away. They’re wrapped totally around the liberty and autonomy values framework and very successfully in the current climate.
The way one other group comes in is through a spokesperson, who at this point represents what I’ll call “communitarianism,” which is about caring for one’s neighbor. Ironically, it’s the Pope—both the previous one and the current one—who speaks out about AI, while the previous one focused on encouraging people to feel duties and obligations toward the weak, the poor, the vulnerable, and migrants and immigrants. Religion was ironically seen as the enemy of medicine. Now it’s providing the moral foundation and is one of the few places doing it for public health interventions.
I don’t think the public gets what public health requires, what it needs, and why it obliges them to do things they don’t normally want to do, which—okay, I understand that I didn’t like being locked in my house either, but that’s been a fear.
One other one is what I’m going to call these eugenics claims. They keep floating around that certain races are inferior or Mexicans are bringing us disease, or there are countries that are “[expletive] countries,” as the President has said, or even some of our tech bro people like Musk insisting that we have to keep an eye on breeding better children so that AI doesn’t overtake us and so on. There is really bad science behind eugenics, and I worry about it being all over the place.
IPM: What will become a hot moral battleground in the future?
Caplan: Everybody expects that the next 10, 20 years will be AI and its incorporation into healthcare, but I don’t think so. Weirdly, incorporating AI stuff into healthcare is, I think, on the whole, pretty useful. It lets you handle a lot of data, get information quickly, and reduces errors. AI skinning or AI surgery or whatever can do certain things better than the human eye or hand.
It’s not that there are no issues. It could turn out to be a huge problem as to whether we can believe any information on the internet or anything anybody posts; that’s a problem, but not within healthcare. I’m going to say “neuroscience,” and I’m going to say “modification of the brain.”
We are learning quite a bit about how the brain works, and right now we are still in the early stages of using needles to control parkinsonism, obsessive-compulsive disorder, or even obesity. That area is going to expand rapidly, raising many questions about how much you can change the brain and still be you, and about the reversibility of some of these changes.
IPM: How will history look back on this period of medical ethics?
Caplan: I think this period will be seen as the dark ages, where science was scrubbed. People were fired for legitimate work, not political reasons. That our history was rewritten to remove important examples of racism in science and medicine. Misogyny. I think we’re in a really miserable period of anti-intellectualism, again, partly spun out of COVID and its disappointments and frustrations. I do think we’re in bad times.
Eli Lilly has expanded its genetic medicines pipeline and capabilities, agreeing to partner with Ascidian Therapeutics to develop RNA exon editors intended to treat inherited kidney diseases, through a collaboration that could generate more than $1.9 billion for the Boston biotech.
The companies have agreed to launch a global research collaboration focused on discovering and developing treatments for undisclosed monogenic kidney diseases, with the option to expand into additional targets.
At the heart of the collaboration are Ascidian’s RNA exon editors, which are designed to repair genetic instructions causing disease. A single RNA exon editor can address multiple mutations spanning multiple exons, resulting in the editing of multiple disease-causing exons simultaneously.
“What that allows us to do is to replace many exons at once, thousands of bases at a time, and use endogenous cellular machinery,” Michael Ehlers, MD, PhD, Ascidian’s president and CEO, told GEN. “We’re not editing letters in the genetic code. We’re rewriting whole chapters at the kilobase scale.
“It’s a very versatile technology to address a fairly wide-ranging set of genetic diseases, and potentially beyond as well,” he added.
Since only exons need to be replaced within the diseased protein, the exon editing payload is small enough to fit in an adeno-associated virus (AAV) or in other viral or nonviral delivery vehicles, including lipid nanoparticles.
Michael Ehlers, MD, PhD, president and CEO of Ascidian Therapeutics [Credit: Kevin Trimmer, courtesy Ascidian Therapeutics]
“The therapeutic is an AAV that expresses the designed RNA exon editor. The AAV infects the target cells. The episome of the AAV dwells in the nucleus and expresses this engineered RNA molecule, our exon editor, that then conducts the trans-splicing,” Ehlers explained. “We very intentionally, across programs and things, really emphasized being a differentiated cargo company in designing these RNAs, and tried where we can to use precedented clinical delivery.”
During the transcription of DNA into RNA, noncoding introns are usually removed, while exons that remain are spliced together to form messenger RNA (mRNA) that can be translated into protein. Mutations result in malformed proteins that cause disease.
Ascidian’s RNA exon editors are designed to bind to target pre-mRNA through what the company calls a highly specific binding domain. The editor molecules are delivered as a DNA construct and transcribed into mutation-free, exon-only RNA, designed with a highly specific binding domain.
Trans-splicing process
Through a binding process called pre-mRNA trans-splicing, exon editors replace disease-causing exons, leading to what Ascidian said is expression of wild-type mRNA and protein at proper levels, in the right cells at the right time.
The exon editors are designed to address large genes or genes with high mutational variance.
“There are other excellent targets which are dominant genes, where maybe you’re uncertain whether the disease-causing mutations are dominant because they’ve got a dominant toxic gain-of-function phenotype, or they’re dominant because it’s a haploinsufficiency. The nice thing about RNA exon editing is that it doesn’t really matter to us. We simply replace the sequence with wild type, so we don’t have to worry about whether you need allele-specific knockdown in those cases, or whether you are at risk of having a haploinsufficiency phenotype,” Ehlers explained.
The exon editing approach, Ascidian said, represents a sea change for RNA therapy, which has seen treatments incorporating antisense oligonucleotides, adenosine deaminase acting on RNA (ADAR)-mediated editing, and mRNA as applied in vaccines such as those for COVID-19, and in in vivo chimeric antigen receptor T-cell (CAR-T) therapies.
“RNA exon editing is really quite different, because you can target and dodge RNAs, and instead of editing one base at a time, you’re changing big swaths of sequence at a time, and unlike a lot of other forms of editing, whether DNA or RNA—not all, but for many—there’s no need to introduce exogenous enzymes or exogenous proteins to be able to conduct the editing,” Ehlers said. “That allows Ascidian to use RNA exon editing to go after a different set of diseases, a different set of disease genes, and potentially a larger patient population.”
In kidney disease, for example, more than 60 genetic diseases are known or suspected to affect the kidneys, with over 3.5 million Americans living with severe inherited kidney disease.
“I would not say all of them are treatable, but a reasonable portion of them are, and we’re prioritizing some that are clearly important, ones where RNA exon editing is particularly uniquely suited, we believe, to addressing the underlying genetic cause,” Ehlers said.
Undisclosed targets
Ascidian has granted Lilly exclusive, target-specific rights to Ascidian’s RNA exon editing technology for undisclosed kidney disease targets. The number of targets was also not disclosed. Ascidian has agreed to lead discovery and specified preclinical activities, with Lilly agreeing to oversee additional preclinical work, clinical development, manufacturing, and commercialization. Ascidian said it retains rights to pursue other kidney-focused targets, independently or with additional partners.
Ehlers said the Lilly collaboration resulted from conversations with the pharma giant held over several years that started with Ascidian discussing its research, and over time became more focused on the companies developing the research plan and programs that they agreed to work on.
“About a year and a half ago, I would say, we kind of got really quite a bit more specific about, well, what would be some interesting areas that might fit with Lilly’s strategic interests and capabilities, where Ascidian’s technology and know-how in RNA biology and splicing biology and using RNA exon editing could apply,” Ehlers recalled.
Genetic medicine expansion
Ascidian’s RNA research and technologies fit with Lilly’s commitment in recent years to expand in genetic medicines. Lilly launched the $700 million Institute for Genetic Medicine in 2021 in Boston’s Fort Point section as part of a strategy of advancing gene and gene editing therapies, and RNA- and other nucleic acid-based therapeutics. The Institute operates in Boston and New York City, where Lilly-owned neuroscience gene therapy developer Prevail Therapeutics is based. Prevail was acquired in 2021 for up to $1.04 billion.
This year, among its numerous acquisition and collaboration deals, Lilly announced plans in February to buy out circular RNA cell therapy developer Orna Therapeutics for up to $2.4 billion, targeting advancements in cell therapy, and last month acquired nonviral DNA delivery-focused drug developer Engage Biologics for up to $202 million cash.
In its latest collaboration with Ascidian, Lilly agreed to pay the biotech up to $1.9 billion, to consist of an undisclosed upfront payment and payments tied to achieving development and commercial milestones, as well as tiered royalties on global commercial sales.
Targeting Stargardt
Ascidian’s website discloses eight pipeline candidates, the most advanced of which is its sole clinical-phase candidate ACDN-01, a first-in-class RNA exon editing therapy designed to halt the progression of Stargardt disease or other ABCA4 retinopathies by targeting their genetic cause.
ACDN-01 contains a healthy copy of exons of ABCA4 RNA, designed to replace the sections of the ABCA4 RNA that contain mutations, thus creating healthy ABCA4 RNA in the retina. According to Ascidian, this is intended to produce normal ABCA4 protein that can then help clear the eye of toxic waste products. The FDA has granted ACDN-01 its Fast Track and Rare Pediatric Disease Designations.
“I anticipate this will be, by and large, the way that we will deliver exon editors. Although, in principle, it can be agnostic to the delivery method, it’s just whatever it takes to get that RNA exon editor into the cell, into the nucleus, effectively trans-splicing at the target.”
ACDN-01 is under study in the Phase I/II STELLAR trial (NCT06467344), an open-label, single ascending dose clinical study assessing the safety, tolerability, and preliminary efficacy of the treatment candidate when delivered subretinally in participants with ABCA4-related retinopathies. Last month, Ascidian said it had completed the adult dose escalation portion of the STELLAR trial and expanded the study to subjects over 12 years of age.
“We’re working as effectively as we can to get that up and going, so I’d say in the coming months,” Ehlers said when asked about the timing of the expansion.
Ascidian is also conducting an observational prescreening study called STARPATH (NCT06445322), which is designed to identify children ages 5+ and adults with Stargardt who may be eligible for future clinical trials evaluating ACDN-01.
ACDN-01 is among numerous candidates in clinical development to treat Stargardt. These candidates include genetic therapies such as:
SpliceBio’s SB-007, a dual AAV gene therapy designed to restore expression of a functional, full-length ABCA4 protein in the retina through a protein splicing intein platform using two AAV serotype 8 (AAV8) vectors to overcome the size limitations of conventional AAVs, reconstituting biologically active ABCA4 through protein trans-splicing in target photoreceptor cells.
VeonGen Therapeutics’ VG801, a dual AAV gene therapy enabled by the company’s vgAAV capsid and vgRNA REVeRT large-gene delivery platform, which delivers the full-length functional ABCA4 gene.
Single vector approach
Ehlers said ACDN-01 would stand out from the other genetic therapies because of its single vector approach to delivery: “I’d say the others, because the nature of the ABCA4 gene, it’s too large just for gene replacement in a single vector. All the others have to use dual vector technologies to try to address that.”
“You can imagine a single vector approach being potentially simpler and more technically feasible,” he added. “But of course, what matters is clinical data, and all these programs will play out in the clinic.”
Also in Ascidian’s pipeline: A second retinal program in lead identification phase; four neuro and neuromuscular programs in phase from lead identification to lead optimization; and two lead identification-phase programs in undisclosed “other areas.” Ascidian is also partnering with Roche to discover and develop RNA exon editing therapeutics against undisclosed neurological targets, through an up-to-$1.842 billion collaboration ($42 million paid initially) launched in 2024.
Following two years in stealth mode, Ascidian was formally launched in 2022 by venture capital firm Apple Tree Partners (ATP), which incubated the company and funded it with $50 million in Series A financing. Ehlers led that incubation as the company’s founding CEO, then chaired the company’s board while Romesh Subramanian, PhD, served as Ascidian’s president and CEO. After Subramanian left the company, Ehlers returned to Ascidian’s helm in 2023, when it closed on $40 million in Series A extension funding from ATP, with the goal of financing the development of ACDN-01 and other pipeline programs.
Since then, Ascidian has grown its workforce to about 40 people, Ehlers said.
“For a clinical stage editing company, to be in the clinic with $90 million in equity financing and have 40 people plus or minus is no small feat, and I think it has been accomplished by having the focus that we’ve had, and having just one of the best scientific teams that I’ve ever had the fortune of working with,” Ehlers said.
“We might have little bits of growth here and there to be able to support this [Lilly] collaboration, to be able to expand the technology, but I’m not anticipating substantial growth,” he added. “We’ve built the company to be efficient and focused, and we’re going to maintain that going forward.”
Lilly’s hot streak
The Ascidian collaboration continues a hot streak of collaboration and acquisition deals for the pharma giant, which is flush with cash from sales of its blockbuster glucagon-like peptide 1 (GLP-1) receptor agonist drug tirzepatide, marketed for type 2 diabetes as Mounjaro® and for obesity as Zepbound®.
So far this year, Lilly has either acquired or is acquiring 10 biotechs, most recently three privately-held developers of vaccines for infectious diseases purchased for a combined up to $3.83 billion cash—Vaccine Company for up to $1.55 billion, Curevo for up to $1.5 billion, and LimmaTech Biologics for up to $780 million.
The Ascidian collaboration is Lilly’s third partnership with a biotech, announced just this week. The other two, totaling a combined amount of up to $4.304 billion-plus, were announced with Asian partners.
Seoul-based Hanmi Pharmaceutical said Lilly had agreed to license from it the rights to develop, manufacture, and commercialize sonefpeglutide (LAPSGLP-2 analog), a Phase II glucagon-like peptide 2 (GLP-2) receptor agonist, worldwide excluding South Korea. Hanmi is now studying sonefpeglutide in a global Phase II trial (NCT04775706) in short bowel syndrome (SBS).
Lilly agreed to pay Hanmi $75 million upfront, and up to an additional $1.185 billion in payments tied to achieving clinical development, regulatory approval, and commercialization milestones, plus royalties on sales following product launch.
Beijing-based Haisco Pharmaceutical Group announced a licensing and research collaboration with Lilly to develop treatments across multiple undisclosed therapeutic areas. Haisco agreed to oversee discovery and identification of up to five “innovative target” programs, while Lilly agreed to lead IND-enabling studies, clinical development, and commercialization. Lilly will obtain exclusive global rights for some programs, as well as exclusive rights worldwide, excluding China, Hong Kong, Macau, and Taiwan, for the other programs.
Lilly agreed to pay Haisco up to $87 million in upfront and near-term payments, up to $2.967 billion in unspecified milestone payments, and single-digit tiered royalties on future product sales.
The all-star lineup of ultra-processed food researchers who teamed up on a new special edition of the American Journal of Public Health have an overarching message for policymakers: “Do policy!”
That directive, offered by food politics scholar Marion Nestle during a press call ahead of the issue’s release, is accompanied by new polling that shows broad cross-partisan concerns over the health harms associated with ultra-processed foods.
A survey of 2,000 U.S. adults included in the new issue found that the overwhelming majority of Democrats, Republicans, and independents agreed that ultra-processed foods are addictive and a major cause of obesity, type 2 diabetes, and cardiovascular disease. The survey also found majority support in all parties for government interventions including testing additives for safety before they can be included in food products, banning artificial dyes, requiring warning labels, and ordering companies to reduce the amount of sugar and salt in their foods.
platform. Lilly also snapped up another gene therapy developer,