<strong>Background:</strong> In recent years, large language models (LLMs) have undergone swift cycles of refinement and iteration. However, in the realm of clinical medicine, different LLMs’ capability of logical reasoning and disease diagnosis needs further investigation. <strong>Objective:</strong> The aim of our study was to evaluate the performance of 4 different LLMs in the National Health Professional and Technical Qualification Examination in China. <strong>Methods:</strong> A total of 398 multiple-choice questions of 5 different question types were integrated within the examination with respect to the diagnosis or care of cases. These questions were categorized into different cardiology subspecialties and different clinical disciplines. DeepSeek V3 and R1 were accessed through an application programming interface, while ChatGPT 4o and o1 were queried via its public chat-based interface. We offered the same prompts instructing LLMs to assume the role of a physician and provide answers with explanations at the beginning of each conversation. We assessed different LLMs’ performance by the accuracy in the responses to the multiple-choice questions. For the first 3 examination sections, McNemar test was used to compare the accuracy among the models, with post hoc pairwise comparisons performed using partitions of chi-square method and Bonferroni correction (significance set at <i>P</i><.008). For the fourth section involving partially credit scoring, one-way ANOVA was performed to compare the mean scores among the models, with statistical significance set at <i>P</i><.05. <strong>Results:</strong> Both DeepSeek V3 and R1 showed superior performance in the first 3 sections of the Chinese National Health Professional and Technical Qualification Examination, achieving an overall performance of 93% and 93.6%, respectively. ChatGPT 4o and o1 achieved accuracies of 73.3% and 69%, respectively (all <i>P</i><.001 compared with DeepSeek V3). For the fourth section, the performance of all 4 LLMs markedly declined compared to their results in the preceding sections. Particularly, in the section of gastroenterology and hematology, DeepSeek V3 achieved the highest accuracy, while R1 ranked first in cardiology and neurology. ChatGPT o1 achieved the highest accuracy in the topic of coronary artery disease, with no statistical significance. <strong>Conclusions:</strong> DeepSeek V3 and R1 showed remarkable potential in facilitating clinical decision-making in the Chinese professional examination, with both outperforming ChatGPT 4o and o1. Nonetheless, future research should continue evaluating their economic efficiency and susceptibility to hallucination.
Although immunoglobulin G (IgG) normally protects the body against pathogens, it can become problematic in many autoimmune diseases like lupus, rheumatoid arthritis, Graves’ disease, myasthenia gravis, and Sjögren’s disease.
“In these conditions, the immune system is creating defective IgGs—called autoantibodies—that are no longer fighting infections,” explained Eric Venker, MD, PharmD, CEO of Immunovant. “Instead, they are attacking a part of your normal functioning body and causing dysfunction.”
Leonard L. Dragone, MD, PhD Disease Area Leader Johnson & Johnson Innovative Medicine.
Historically, autoimmune conditions have been challenging to treat because therapies like steroids rely on broad immune suppression, noted Leonard L. Dragone, MD, PhD, disease area leader of autoantibody and rheumatology at Johnson & Johnson Innovative Medicine. These non-specific approaches are often inconsistently effective and lead to adverse side effects.
“For many autoimmune diseases, there is a need for more targeted strategies that address disease-causing autoantibodies directly, rather than broadly suppressing the immune system,” emphasized Dragone. Beginning in 1998, the U.S. Food and Drug Administration (FDA) approved infliximab, a tumor necrosis factor (TNF)-α inhibitor, for the treatment of Crohn’s disease. This marked the first approval of a monoclonal antibody for the treatment of a chronic condition. Since then, targeted therapies for autoimmune diseases have expanded to address cytokine signaling pathways (TNF-α, IL-6, IL-17, IL-23), Janus kinase (JAK–STAT) signaling, and immune cell surface markers (CD20).
Another such targeted strategy involves an emerging drug class called FcRn blockers, which are now showing considerable promise in the treatment of certain autoimmune diseases.
FcRn blockers, which typically consist of monoclonal antibodies or antibody fragments, work by blocking the function of a protein receptor called FcRn (neonatal Fc receptor). This prevents IgG recycling, thereby reducing IgG levels in the body.
FcRn maintains levels of IgG in circulation by preventing IgG degradation in the lysosomes of cells. However, FcRn drugs block this pathway.
Venker compares FcRn inhibitors to cholesterol-lowering drugs such as statins. “LDL is the disease-causing agent that healthcare providers target to prevent many cardiovascular diseases. Likewise, in the case of FcRn blockade, we are aiming to lower IgG. We believe that deeper IgG reduction may provide improved results.”
As of early 2026, the FDA has approved three FcRn inhibitors for the treatment of myasthenia gravis, a chronic autoimmune disorder affecting up to 100,000 people in the U.S. Efgartigimod (approved in 2021), rozanolixizumab-noli (approved in 2023), and nipocalimab-aahu (approved in 2025) all work by reducing pathogenic IgGs associated with the disease.
Myasthenia gravis results from harmful antibodies (anti-AChR or anti-MuSK) produced by the immune system that interfere with signaling in the neuromuscular junction.
“With FcRn blockers, it is exciting to know that there is now a targeted mechanism for patients around the world with autoimmune diseases caused by an IgG autoantibody,” said Venker.
Tackling Graves’ disease
In Graves’ disease, an IgG autoantibody called thyrotropin receptor antibody (TRAb), which targets the thyroid-stimulating hormone (TSH) receptor of the thyroid, is produced. The condition, which is the most common cause of hyperthyroidism, causes elevated heart rate, shakiness, irritability, muscle weakness, and weight loss.
“TRAb is an IgG antibody, but it is a badly behaving one that is basically hijacking the thyroid system,” noted Venker. “It doesn’t serve any purpose that is normal at all.”
Mark A. Lupo, MD Founder and Medical Director Thyroid & Endocrine Center of Florida
Unfortunately, the toolkit for treating Graves’ disease hasn’t changed much since 1950, when the FDA approved the drug methimazole, said Mark A. Lupo, MD, founder and medical director of the Thyroid & Endocrine Center of Florida.
Methimazole is an anti-thyroid drug that slows down the production of thyroid hormones. Although Graves’ patients benefit from anti-thyroid drugs, Lupo estimates a 50% relapse rate within two years of discontinuing these drugs.
Other options for treating Graves’ disease include surgical removal of the thyroid or the use of radioactive iodine to induce destruction of the thyroid gland. However, these approaches result in permanent hypothyroidism, and patients typically require lifelong thyroid hormone replacement after treatment.
Because TRAb is an IgG, FcRn drugs represent a potential autoimmune solution for Graves’ disease. Like all FcRn blockers, they may work by decreasing TRAb recycling and lowering TRAb levels.
Lupo highlights Immunovant’s recent proof-of-concept study of an FcRn inhibitor for Graves’ disease, the first such study for the condition. “Despite the small number of patients (around 25), the results from this study suggest a potential, durable remission six months off treatment,” said Lupo.
While study participants experienced an increase in total IgG levels following treatment, TRAb levels remained low over a six-month period. The thyroid also decreased in size. “To see TRAb levels down six months off the study drug caught the attention of the endocrine thyroid community,” noted Lupo.
“What was unexpected was that TRAb, the disease-causing antibody, stayed down for many months after stopping the investigational therapy,” added Venker.
“I think we are overdue for a new option in Graves’ disease that could help break some of these methimazole cycles and potentially address not the innocent thyroid gland but the underlying immune system issues,” concluded Lupo.
But are they safe?
Venker recalls that safety was an initial concern with FcRn inhibition. After all, these drugs work by reducing IgG, an essential part of the immune system. “Any time you are using an autoimmune drug that potentially suppresses your immune system, you have to think about going too far. Am I going to cause an infection or weaken the immune system?
“So far, this investigational drug has demonstrated a safety profile we expected, and appears positive,” noted Venker. “That makes sense mostly because FcRn blockade is pretty targeted.”
“Although there are no head-to-head comparative safety trials yet, most clinicians and principal investigators view FcRn blockers as relatively safe,” added Lupo. “There are FcRn blockers on the market, and they have demonstrated a good safety record in patients.” The most common side effect tends to involve injection site reactions with either intravenous or subcutaneous delivery.
Preventing fetal exposure
During pregnancy, maternal antibodies—called alloantibodies—can cross the placenta and attack the organs and tissues of the fetus, explained Dragone.
A distinguishing feature of Johnson & Johnson’s nipocalimab is its pH-independent binding to FcRn. This allows it to bind with high affinity in the placenta, a low-pH environment.
The drug is currently showing potential in the treatment of two alloimmune diseases of pregnancy: hemolytic disease of the fetus and newborn (HDFN) and fetal and neonatal alloimmune thrombocytopenia (FNAIT), said Dragone. These conditions can arise during alloimmunized pregnancies, when the pregnant person’s immune system forms alloantibodies against fetal red blood cells (HDFN) and/or fetal platelets (FNAIT). Importantly, published data on nipocalimab suggest minimal transfer of the drug to the fetus or infant. “Therapies like nipocalimab offer a blueprint for how precision medicine can expand to include pregnant people, a population that has historically been excluded from drug development,” noted Dragone. “Our approach with nipocalimab has the potential to change how we think about treating autoantibody-driven diseases in people of childbearing age.”
Nipocalimab (IMAAVY®) and other FcRn blockers bind to FcRn receptors and reduce levels of both normal and harmful IgG antibodies.
The FDA has granted a fast track designation to nipocalimab for both FNAIT and HDFN, and Phase III studies are underway to further investigate the drug in both diseases.
Expanding indications
“There are probably 20 trials out there for FcRn blockers, and many are likely to work,” noted Venker. “There are a ton of potential new indications under investigation, including rare diseases that have been ignored historically.”
He notes that Immunovant’s pipeline alone includes potential indications in endocrinology (Graves’ disease), rheumatology (rheumatoid arthritis, Sjögren’s disease, and cutaneous lupus erythematosus), and neurology (myasthenia gravis and chronic inflammatory demyelinating polyneuropathy).
Venker stresses that no FDA-approved solutions exist for Sjögren’s disease, which affects as many as four million Americans. The condition causes severe dry eyes and mouth, fatigue, and joint and muscle pain. Immunovant and Johnson & Johnson are conducting clinical trials to evaluate FcRn blockers for the disease.
Hani Houshyar, PhD Strategy Team Lead argenx
Meanwhile, argenx’s FcRn inhibitor efgartigimod has been used in 19,000 people worldwide for myasthenia gravis and other autoimmune conditions, said Hani Houshyar, PhD, FcRn asset strategy lead for argenx.
“However, we believe myasthenia gravis is just the beginning,” she said. As of 2026, the company has active clinical trials to test the drug’s effectiveness in additional autoimmune diseases with high unmet medical need, like myositis, Sjögren’s disease, ocular myasthenia gravis, systemic sclerosis, Graves’ disease, and autoimmune encephalitis.
UCB’s rozanolixizumab was the first FcRn blocker to be approved for the treatment of generalized myasthenia gravis in adults who are positive for anti-AChR or anti-MuSK antibodies, who together account for approximately 90% of cases, said Omar Sinno, MD, UCB’s U.S. medical strategy lead of rare disease. So far, the drug has been approved in the U.S., Canada, the EU, Australia, Switzerland, China, Turkey, and Korea.
Omar Sinno, MD Medical Strategy Lead, UCB
Rozanolixizumab is administered via a convenient subcutaneous infusion rather than intravenously. The company’s long-term studies demonstrate robust IgG reductions (up to 75%) with sustained benefit across multiple treatment cycles. UCB is also investigating rozanolixizumab as a potential treatment for a rare autoimmune condition called myelin oligodendrocyte glycoprotein antibody-associated disease.
Finally, Johnson & Johnson’s nipocalimab is in mid-to-late-stage studies for Sjögren’s disease, lupus, warm autoimmune hemolytic anemia, and chronic inflammatory demyelinating polyneuropathy.
Drugs in development
Viridian Therapeutics is currently investigating two FcRn inhibitors, VRDN-006 and VRDN-008, said Steve Mahoney, president and CEO. Both candidates are designed as subcutaneous products that can be conveniently self-administered by the patient.
Steve Mahoney President and CEO Viridian Therapeutics
VRDN-006 is an Fc fragment in Phase I trials, while VRDN-008 is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression. Mahoney notes that VRDN-008 showed a longer half-life and more sustained IgG reduction than efgartigimod in a high-dose, head-to-head study in non-human primates.
Clinical trial results of VRDN-008 in healthy volunteers are expected later in 2026. “What we believe differentiates VRDN-008 from other FcRn inhibitors is a longer half-life, which has the potential to support less frequent dosing for patients to enhance convenience,” said Mahoney.
Although three FcRn blockers are currently FDA-approved to treat myasthenia gravis in the U.S., Venker notes that Immunovant is continuing to investigate the condition with the company’s follow-on FcRn candidate, imeroprubart (IMVT-1402).
In Immunovant’s proof-of-concept study for Graves’ disease, TRAb stayed low even six months after the investigational treatment was discontinued. But how long will this effect last? “We don’t know that yet because our randomized trials with IMVT-1402 are ongoing,” Venker said. “However, Graves’ disease has given us the first hint that FcRn drugs may be able to put certain autoimmune conditions into permanent remission.”
Viridian’s VRDN-006 (top) is an Fc fragment, whereas VRDN-008 (bottom) is made up of an Fc fragment and an albumin-binding domain designed to prolong IgG suppression.
“A key question for autoimmune disease, the holy grail, so to speak, is whether we can reset the immune system so the person can function normally without medication for the rest of their lives,” he added.
Finally, argenx is developing ARGX-213, a next-generation FcRn inhibitor engineered to extend half-life and sustain IgG reduction.
“Looking ahead, FcRn inhibition represents an increasingly important approach across IgG-driven disease,” noted Sinno. “By selectively reducing pathogenic IgG, these agents enable more targeted autoimmune care. And as clinical experience with FcRn inhibition grows, treatment paradigms may shift toward earlier intervention.”
Tiffany Yesavage, PhD is a freelance writer from Denver, Colorado.
Since the first in vitro fertilization (IVF) baby was born in 1978, the options for couples or individuals struggling with infertility have improved exponentially. However, the core methods that make up this process are still fairly crude and associated with significant discomfort and side effects. This is something that reproductive endocrinologist Marie-Christine Maurel, PhD, chief scientific officer (CSO) and founder of Igyxos Biotherapeutics, is hoping to improve with the company’s first‑in‑class antibody treatment for infertility.
The antibody treatment—IGX12—amplifies the body’s own follicle-stimulating hormone (FSH) signal in both women and men, potentially improving production of both sperm and eggs with fewer injections than IVF and more physiological control.
Maurel has a doctorate in reproductive physiology from Pierre & Marie Curie University in Paris and worked as a post-doctoral fellow at the Pasteur Institute in Paris. The idea for the infertility treatment, which achieved promising Phase I results at the end of last year, originated from work at Maurel’s first biotech firm ReproPharm, which she co-founded in 2009 after winning a French “national competition for the creation of innovative companies.”
Maurel previously worked at the National Institute of Agronomic Research (INRA) near Paris for more than 25 years. Her group studied how gonadotropins affect fertility in animals and developed monoclonal antibodies that impact the activity of these reproductive hormones. ReproPharm initially used this research to improve fertility in farm animals, but when the team realized the same ideas could be applied to human infertility, the initial company was split into ReproPharm Vet and Igyxos in 2017 to focus on animal and human fertility problems, respectively. Alongside serving as CSO at Igyxos, Maurel remains president and CEO of ReproPharm Vet.
Maurel discussed her inspirations, research, and motivations for founding both companies with Inside Precision Medicine’s senior editor, Helen Albert, and outlined why Igyxos’s antibody could be so important if it achieves market authorization.
Q: What inspired you to become a scientist?
Marie-Christine Maurel, PhD
Maurel: When I was younger, I was passionate about science, and biology in particular. In my teens, I hesitated between choosing to study medicine or biological research. Finally, I chose biological research, but remained very interested in biomedicine. Currently, I mix both topics because we are developing a new medicine to treat infertility problems in humans, so it’s a mix of research and medicine. I still enjoy scientific research, so I don’t regret my decision.
Q: You worked in academia for a long time before you decided to make the move into industry. What inspired you to do that?
Maurel: In nature, there are lots of things that occur. You just have to discover them and know how to ask the right questions to understand how they work. Penicillin is an extraordinary example. And here it’s the same thing. We were doing experiments with sheep and goats. When we discovered that the ewes or does that secreted potentiating antibodies were hyper prolific and had high numbers of offspring, we wondered why. Normally, antibodies block the activity of a hormone and never enhance it. But in this case, we discovered that these particular antibodies were able to potentiate the activity of reproductive hormones. It was a marvelous result because it meant [that] it was possible to avoid the use of hormone treatment in animals. When my team and I discovered the existence of these potentiating antibodies, I quickly assessed their potential for application in both human and animal health. I wanted to develop and translate the research. The fact that there are potentiating antibodies for FSH is extraordinary, because antibodies are normally always inhibitory. I wanted to develop a potentiating antibody so we could have much more effective treatments for infertility. I also won a national competition for the creation of innovative companies, which helped with founding ReproPharm. It was a wonderful adventure to create a new biotech with our innovation.
Q: What did you learn from the experience of founding ReproPharm?
Maurel: I learned a lot of things. It was a human experience. I met a lot of people in medicine and industry who were very important for the development of the company and myself as well. These people helped me to build and to progress the company. Building a good network was important for me when I went into industry. I would also advise this for young people who want to create a biotech company. Meeting good people helps enormously!
Q: What made you decide to split ReproPharm into the two spinout companies, ReproPharm Vet and Igyxos Biotherapeutics?
Maurel: My research group was based at INRA initially. It’s a French academic research center focused on animal reproduction. We started with an animal reproduction problem linked to breeding ovine and caprine species, but early on, we tried our innovation on human hormones because we thought it could be an excellent approach to treat infertility problems in women. We developed an antibody against human FSH to see if we could enhance the activity of human FSH and in animal species. We got some money to carry out the first experiments and had very good results. We then decided to develop this innovation in human health, but needed more funds to develop it further. All our existing investors told us that they were unwilling to take the risk of investing in a company developing both veterinary and human medicine. It was impossible for them because it was not separated, so we decided to split the first company into two independent companies in 2017.
Q: Did any of your experiences at ReproPharm help you to do things better at Igyxos?
Maurel: First, I can say that at Igyxos, from the experience with ReproPharm, I wanted to do as much research and development on IGX12 as possible using our own funds, and license the therapy as late as possible because that gives us more freedom to develop it as we want to. I think it is necessary to be independent as long as possible for this reason.
Also, during the founding and development of ReproPharm, we developed a lot of animal models, which are very useful now to develop IGX12 for treating human infertility, both in men and women. So it was a very strong basis for Igyxos. All these animal models we developed at ReproPharm were important for developing IGX12 and getting it to clinical trials.
Q: Can you tell me a bit more about what you’re trying to achieve at Igyxos?
Maurel: FSH is exactly the same hormone in men and women. It has different target cells, but the molecule is the same. So one potentiating antibody could act on FSH either in men or women. It’s exactly the same mechanism of action, so we can develop the first treatment in men with oligozoospermia, for example.
We also want to develop a new and innovative treatment for women with infertility, which could be more efficient than current treatments that are burdensome and costly. Now it’s necessary to repeat the same hormone treatment four or five times to have a baby with a 50% chance of success. We think that it will not be necessary to repeat our treatment because we have a lot of proof of concept in animals. We have shown we can get better gametogenesis with better quality of ovulation than other methods.
Q: You reported Phase I results in December 2025. Were you happy with the findings?
Maurel: Yes, it was totally successful. We got very nice results. No adverse events, and we have some first efficacy results, so we can start Phase II trials, but we need to raise money first.
The trial results have helped to interest investors, and we are now in contact with several funds. If the fundraising is successful, we hope to be able to start Phase II trials soon.
Q: You mentioned that IGX12, if approved, would be the first such treatment for men with common fertility issues like oligozoospermia. Why have more treatments not been developed for men before?
Maurel: The problem of male infertility was not considered for a long, long time, perhaps because of cultural issues. Now there is a huge problem with infertility in men because sperm counts are decreasing. Numbers decreased from around 100 million per mL to 50 million per mL between 1973 and 2018. So this treatment is very necessary!
Q: Do you think that if your treatment is successful, it could make IVF more accessible?
Maurel: Yes, I think that it would allow a reduction in both time and economic cost, because as I said previously, the treatment will be more efficient, so no need to repeat it. We developed the concept that the antibody could act on the endogenous FSH. So, using our approach, it would not be necessary for women to inject FSH, because the antibody is able to boost the woman’s own FSH. In the animal health domain, we use the antibody only. We never inject endogenous hormones, so it’s very clean. In humans we will also only inject the antibody. We never inject FSH. So it’s a single injection per month. If we succeed, it’s a very big market and a very nice treatment for a lot of people.
Q: Could IGX12 make fertility treatment more targeted for specific people or certain population groups?
Maurel: Yes, for example, men with oligozoospermia. That means the sperm count is too low for natural conception. If it’s a very low level, it’s not even possible to do IVF. So we will target this category of men. In women, we will target those who don’t have a good predicted result with IVF, for example, if they have a low follicular count. So we plan to target these two populations, which have few chances to succeed at having children with current treatments.
Q: What are your future plans for Igyxos and ReproPharm Vet?
Maurel: For Igyxos, the current priority is to raise funds to start Phase II clinical trials, both in men and women. For ReproPharm Vet, the objective is to conclude an ongoing collaboration with a big veterinary and pharma partner.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at the Sanger Institute in Cambridge before deciding to move into journalism.
As a postdoctoral researcher at the University of Pennsylvania, Haijiao Liu, PhD, helped advance tumor-on-a-chip technology, a feat of bioengineering that mimics the microenvironment of malignant human tumors. Led by Dan Dongeun Huh, PhD, a Penn Engineering professor and trailblazer of organ-on-a-chip technology, Liu and his team explanted lung adenocarcinoma tumors onto the transparent chips to test their perfusion with chimeric antigen receptor (CAR) T cells. Their findings were published in October in Nature Biotechnology, with Liu as first author.
Now on paternity leave in Toronto, Liu spoke with Lindsey Leake about the implications of this work, the challenges inherent to tumor-on-a-chip studies, and his plans to launch a lab of his own this fall.
Q: Walk me through the creation of the tumor-on-a-chip. What went into its design?
Haijiao Liu: It’s essentially inspired by the need for alternative tumor models. This is speaking to the traditionally used animal tumor models and some existing in vitro tumor models, especially for the study of immunotherapies.
For example, when I started at Penn around 2018, Penn Medicine was pioneering this immunotherapy called CAR T-cell therapy, which is basically aiming to harness the patient’s own immune system, specifically the patient’s own T cells, to help fight the cancer. Penn Medicine was demonstrating huge clinical success using this CAR T therapy to treat blood cancers, such as leukemias and lymphomas. In a huge contrast to this, the solid cancer arena has seen a limited response from this new immunotherapy. So there’s this great need to study why this has not been successful, and that comes down to the consensus that the solid tumor has this really complex microenvironment.
In the category called tumor-on-a-chip, people try to control the cultural environment, the biochemical and biophysical environment of tumor cell cultures. We can use this for simple drug testing—see how the tumor growth will be affected or how effectively they can be killed. However, these existing tumor-on-chip or in vitro tumor models are still very simple. They don’t usually recreate or reproduce the complex structure of the human solid tumors that I described, like where they often include complex vessel networks.
I took the lead to address the need and the challenges of reproducing and then investigating, or probing, the dynamic interactions between those CAR T cells and human solid tumors entirely in vitro.
Q: How does the vascularization work on the chip?
Liu: It took several years to start, from the idea of building this more advanced tumor-on-a-chip technology toward proving it’s actually useful. I started by focusing on this one aspect, which is the CAR T-cell trafficking and their functions after they traffic to fight the tumors, and that will involve the recreation of the structural interface between the tumor and this complex vascular network that’s present in human tumors.
I was inspired by in vivo tumor transplantation, where traditionally, people take human tumors and then transplant them in a bulk, intact format into animal models. So my idea was, if we want to focus more on the human biology, if we want to engineer this entirely in vitro, how about we design a vascular bedding, like a miniature living model?
We basically took advantage of the self-assembly capability of human-sourced endothelial cells, combined with certain stromal fibroblasts, or stromal cells. With a bit of optimization, engineering, tweaking, then we can allow them to form capillary-like vascular networks in our engineered models.
Q: What are the advantages of recreating the tumor microenvironment in this way? That is, is the Petri dish becoming obsolete in cancer research?
Liu: The unique advantage of this way of engineering is to have a higher level of control over the structures of the tissue-tissue interface that we can build. For example, we can engineer different culture chambers. We can engineer different access windows with this model. That allows us to construct, step by step, the vascular bedding and then the tumor transplantation. Also, by forming these perfusable vessels—by the way, we can provide the infusion and flow of the CAR T cells, just like they are infused and flow in the patient—that gives us the leverage to reconstruct, probe, and then control these tissue functions in a highly precise manner.
Q: How did you and your colleagues at Penn explore CAR T-cell activity on the chip?
Liu: We first used different functional assays, like immunostaining and ELISA (enzyme-linked immunosorbent assay) assays, to characterize how the CAR T cells are doing and how they are interacting with the tumors in our engineered model. Then we disassembled this engineered tissue to extract all the cells for flow cytometry, to further characterize their functional phenotypes.
With the help of our collaborators and other people in the lab, I took advantage of this engineered model of vascular tumors interacting with CAR T cells for multi-omics analysis. For example, I was able to extract all the cells and send them for single-cell RNA seq[uencing]. We were able to look at the gene expressions of each individual cell from all the cell types that we included in this model. In this way, we have almost like a superpower to probe and read into how each cell—including the CAR Ts and tumors and the vessels—how they are responding and interacting with each other at the molecular gene levels. This is so powerful that it helped me to discover novel interactions between these parties and also new druggable targets.
The message is that through the development of this more advanced tumor-on-a-chip technology—combined with advanced multi-omics analytics and advanced computational analysis—we were able to provide this powerful in vitro technology to apply to accelerate the development of cell therapies, such as the CAR T immunotherapies for cancer, but also other complex diseases.
Q: What are the overall implications of this latest research?
Liu: With a growing understanding of human biology at the cellular and tissue levels, I think we’re seeing that our ability to engineer and design biological systems is also growing. More than ever, we have these advances in the ability to precisely construct, investigate, and then eventually control very complex tissue functions, and even organ functions. For example, our demonstrated tumor-on-a-chip technology is like presenting a miniature sandbox; we can literally see and predict the battlefield of CAR T therapy in cancer.
If we combine these advanced engineering technologies with emerging technologies in spatial multi-omics and the unprecedented productivity of the AI revolution, we will be able to accelerate the understanding of more complex human biology and extract more biological insights, and then apply that to accelerate the development of safer and more efficacious drugs and therapies, such as immunotherapies in cancer.
Q: What are the limitations of organ-on-chip technology that need to be overcome?
Liu: I think there are challenges on two fronts. The first limitation is the lack of complexity. We’re claiming that what we just published is a sufficiently complex system for us to deeply probe and understand the dynamics of CAR T tumor interactions. Still, if we’re speaking next level of translational power or potential, then we need to pursue a higher complexity that incorporates the missing but critical components from in vivo.
The other side of the coin is that if you make this engineered model more complex, you make it more challenging to reproduce or to scale up or to translate to other labs. But also, that points to an opportunity and growing room for translation, to standardize every single step, from the construction to the analysis of these engineered models, and to automate these processes as much as possible.
Q: What do you envision for your new lab?
Liu: I have a lot of things I want to do. I’m eager to establish my own team. The overarching and the unifying theme of the new lab will be to develop the next generation of in vitro complex tissue models, or I call it assembloid tissue models. Assembloid basically means there’s a stem cell-based, three-dimensional complex tissue model that intentionally incorporates different cell types, to emulate the critical tissue-tissue interactions that determine the tissue- and organ-level functions. I still need to make a big decision where the lab could be; it could be in Canada and it could also be in China.
Q: What impact might tumors-on-a-chip have on the future of precision medicine?
Liu: It’s attracting a lot of attention from biologists and clinicians who are heavily focused on using the traditional tissue models—animal models, for example, or the simple dish cultures—for their studies of interest. So the biggest impact I can foresee with our technology is that now it’s more mature. I can see it being gradually, and maybe quickly, adapted into more traditional biological labs, to help them dissect the complex biological questions they’re asking, or to accelerate the evaluation of the exciting new drugs or therapies they’re developing. Overall, I can see that accelerate this development pipeline of new drugs and therapies in precision medicine.
Lindsey Leake is an award-winning, independent health reporter based outside Washington, D.C. She spent 15 years as a staff journalist at outlets including Fortune, the USA TODAY Network and Sinclair Broadcast Group. She holds an MA in Science Writing from Johns Hopkins University, an MA in Journalism and Digital Storytelling from American University and a BA from Princeton University.
Researchers at Baylor College of Medicine have identified a mechanism driving progressive heart disease in people with myotonic dystrophy type 1 (DM1) that operates independently of genetic repeat expansion, providing new evidence of how cardiac damage develops and when it may be reversible. The study, published in the Journal of Clinical InvestigationInsight, shows that sustained expression of expanded CUG (CUGexp) repeat RNA drives cumulative cardiac injury through structural remodeling, including myocardial fibrosis, chamber dilation, and impaired contractility, while also disrupting electrical conduction pathways that regulate heart rhythm.
“Cardiac manifestations affect most DM1 patients,” said corresponding author Thomas A. Cooper, MD. “Cardiac problems are primarily electric conduction abnormalities, seen in up to 75% of adult DM1 cases, which can result in life-threatening arrhythmias accounting for 25% mortality and the second leading cause of death in DM1.”
DM1 is an autosomal dominant disorder and the most common cause of adult-onset muscular dystrophy. It is caused by an expanded CTG repeat in the DMPK gene, with affected individuals carrying between 50 and more than 4,000 repeats, compared to five to 37 in unaffected individuals. The expanded CTG repeat causes mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. The result is a loss of function of MBNL.
DM1 affects multiple systems, including skeletal muscle, the central nervous system, the gastrointestinal tract, and the heart. Cardiac impairment is common in people with the disease and is often fatal. Electrical conduction abnormalities, including prolonged PR, QRS and QTc intervals, atrioventricular block and bundle branch block, occur in up to 75% of adults with DM1. Patients may also develop atrial fibrillation, tachycardia and, less commonly, ventricular arrhythmias. Structural changes such as left ventricular dysfunction, hypertrophy, dilation and fibrosis contribute to morbidity and mortality. These conditions typically worsen with age and are more severe in males.
The Baylor team used a transgenic mouse model engineered to express toxic CUG repeat RNA in the heart. Unlike human disease, the number of CTG repeats in this model remained stable over time, allowing researchers to isolate the effects of prolonged RNA toxicity without the confounding factor of repeat expansion. The researchers measured the cardiac function of the mice over a period of 14 months.
According to the researchers, the data showed that “sustained CUGexp RNA expression caused progressive cardiac enlargement, contractile dysfunction, conduction delay, myocardial fibrosis, and reduced survival, while MBNL-dependent splicing defects remained static, consistent with the stable repeat length.” These findings indicate that cardiac deterioration can occur even without increasing loss of MBNL function. This finding runs contrary to current thinking, which centers on the role of repeat expansion as the primary driver of disease progression.
In this research, the model mice developed enlarged hearts and electrical abnormalities early on. Over time, these changes progressed to cause weakened cardiac function, fibrosis and dilation of heart chambers.
The study also sought to find whether the cardiac damage could be reversed by halting expression of the toxic RNA. When RNA expression was stopped after a short duration, heart size, electrical function and structure largely returned to normal.
Yet when exposure to the toxic RNA was prolonged, the mice did not exhibit complete recovery. While the molecular defects such as abnormal RNA splicing were fully corrected, structural damage, including fibrosis and conduction abnormalities, persisted. This shows that early intervention could be one method to prevent irreversible changes such as fibrosis, which disrupts electrical signaling and increases the risk of arrhythmias.
Prior research had linked increasing CTG repeat length with DM1 severity and earlier onset, but the extent to which other mechanisms contribute to progression remained unclear. By isolating RNA toxicity, the Baylor researchers have provided evidence that chronic cellular stress, structural remodeling and potentially other RNA-mediated effects play roles in disease pathology independent of repeat expansion.
Future research will look to identify any additional mechanisms that may contribute to disease progression, and will include studying the long-term effects of RNA toxicity, changes in RNA-binding proteins, and potential links to premature cellular aging.
Studying sexually transmitted infections (STIs) has long been constrained by a fundamental problem: the available models fail to fully capture the complexity of the human body. Traditional cell cultures oversimplify biology, while animal models often do not accurately reflect human infection dynamics.
Now, scientists at the University of Maryland School of Medicine and collaborators have developed the first immune-capable “cervix-on-a-chip,” a microengineered system that recreates the human cervical environment with unprecedented realism. The work, published in Science Advances, could significantly accelerate the development of new treatments and prevention strategies for STIs.
A long-standing gap in STI research
STIs remain a major global health burden. According to the World Health Organization, nearly one million new infections occur every day worldwide, with chlamydia alone accounting for roughly 129 million cases annually. In the United States, chlamydia and gonorrhea together generate an estimated $1 billion in direct medical costs each year.
Beyond their prevalence, these infections can lead to serious complications, particularly in women, including infertility, pelvic inflammatory disease, and adverse pregnancy outcomes.
Despite this, researchers have struggled to study how infections develop and progress in the human cervix, a key site of infection, under realistic conditions.
“This new model will revolutionize how scientists study STIs,” said Jacques Ravel, PhD, co-lead author of the study. “By integrating engineering, microbiology, immunology, and microbiome science, we were able to build a model that more closely reflects human biology and the complexity of the cervical microenvironment.”
Recreating the cervix in the lab
The newly developed system belongs to a class of technologies known as organ-on-a-chip models, or microphysiological systems. These platforms are designed to mimic the structure and function of human tissues using living cells and controlled physical environments.
In this case, the researchers constructed a miniature model of the cervix using human cervical epithelial cells layered on a porous membrane, with supportive tissue cells beneath. Fluids flow across both sides of the membrane, replicating the dynamic conditions found in the body.
The model also incorporates immune cells and microbial communities, allowing scientists to study how these components interact during infection.
“A key goal was to develop a complex model system that is both practical and accessible,” said Jason Gleghorn, PhD, who led the model development. “The need for this model was particularly critical for studying the vaginal microbiome, which we know plays an important role in susceptibility to STIs.”
Capturing the role of the microbiome
One of the defining features of the cervix-on-a-chip is its ability to include different types of vaginal microbiomes, something that has been difficult to replicate in previous models.
The researchers tested the system using two of the most common STIs: chlamydia (Chlamydia trachomatis) and gonorrhea (Neisseria gonorrhoeae). They found that the outcome of infection depended strongly on the type of microbiome present.
In models dominated by Lactobacillus crispatus, a bacterial species commonly associated with vaginal health, infections were significantly limited. In contrast, when less protective microbiomes were introduced, infections became more severe.
“One of the most exciting findings was that just like in women, protective microbiomes dominated by Lactobacillus crispatus limited infection in the model,” Ravel said. “In contrast, when we introduced ‘nonoptimal’ microbiomes, infections worsened.”
These results reinforce growing evidence that the vaginal microbiome plays a central role in determining susceptibility to STIs.
Toward better treatments—and prevention
Beyond improving understanding, the new model provides a practical platform for testing potential therapies.
Because it closely mimics human biology, the cervix-on-a-chip can be used to evaluate new treatments under realistic conditions. This includes not only traditional antimicrobial drugs but also emerging approaches such as probiotics and live biotherapeutics designed to restore protective microbiomes.
“This model provides a powerful new tool to develop faster, more effective, and personalized treatments,” Ravel said. “For the first time, we can simulate what happens in the human body rather than relying solely on petri dish systems or inadequate animal models.”
A platform for broader applications
The implications of the technology extend beyond the infections tested in the study. The cervix-on-a-chip could be adapted to study a wide range of pathogens, as well as broader questions about reproductive health, inflammation, and host–microbe interactions.
The researchers emphasized accessibility in the model’s design, aiming to make it usable by scientists outside of specialized bioengineering labs. This could accelerate adoption and expand its impact across the field.
A step toward more human-relevant science
The development of immune-capable organ-on-a-chip systems represents a broader shift in biomedical research toward more human-relevant experimental models. By integrating multiple components of human biology—cells, tissues, immune responses, and microbiomes—these systems offer a more accurate view of disease processes.
In the context of STIs, where subtle interactions between host and microbes can determine outcomes, such realism is particularly valuable.
As researchers continue to refine these platforms, they may help bridge the gap between laboratory studies and real-world biology—ultimately enabling earlier, more precise, and more effective interventions.
For now, the cervix-on-a-chip marks a significant step forward, providing scientists with a tool that captures the complexity of the human cervix in a way that was previously out of reach.
Research led by Osaka International Cancer Institute in Japan shows that rates of therapy-related acute myeloid leukemia, linked to treatment for an earlier cancer, are going up as the overall number of cancer survivors increases.
As reported in the journal Cancer, the researchers showed the rates of treatment-related acute myeloid leukemia (AML) almost tripled between 1990 and 2020. The share of overall AML cases taken up by these patients has also increased from 4.4% to 8.2% over a similar time period.
With increasing numbers of cancer survivors in the U.S. and elsewhere, understanding the adverse effects of cancer treatment is becoming increasingly more important. Therapy‑related AML is a rare but serious complication of cytotoxic chemotherapy, and different chemotherapy drugs carry different levels of leukemia risk. Radiotherapy can also lead to this condition, but the risk is considered lower than that of chemotherapy.
“Several population‐based studies have analyzed the long‐term trend of therapy-related AML incidence, and the results are controversial,” write lead author Kenji Kishimoto, MD, PhD, a researcher at the Osaka International Cancer Institute, and colleagues.
“A national population‐based study did not demonstrate an increase in the incidence of therapy-related AML in Denmark between 2000 and 2013. In contrast, a significant increase in therapy-related AML incidence between 1997 and 2015 was identified in a Swedish nationwide study.”
As few such studies have been carried out in Asia, Kishimoto and colleagues analyzed how such rates have changed over time and whether the initial cancers leading to therapy-related AML have changed in Japan.
The researchers identified 9841 patients with AML in the Osaka Cancer Registry, 636 (6.5%) of whom had therapy-related AML. These patients were older when diagnosed than other AML patients at a median of 69 versus 66 years. There were also slightly more women with therapy-related AML than standard AML at 45% versus 40%. The time lag between first cancer and resultant AML was between two and 11 years (median five years).
In 1990, the incidence of therapy related AML was 0.13 per 100,000 people, but this had increased to 0.36 per 100,000 people by 2020. The share of all AML cases made up by therapy-related cases almost doubled from 4.4% in 1990 to 8.2% after 2010.
The most common earlier cancers before therapy-related AML were blood cancers (23%), breast cancer (15%), colorectal cancer (12%), and gastric cancer (9%). The mix shifted over time and gastric cancer became less common as the first cancer, while breast, head‑and‑neck, and lung cancers became more prominent.
“The study provides an important step towards better understanding how the nature of therapy-related AML is changing with the increasing number of cancer survivors,” said Kishimoto in a press release.
“Findings from this study lay the foundation for further studies to elucidate the mechanism of the change in therapy-related AML epidemiology,” add the authors.
Central nervous system (CNS) treatments are having a major comeback. These five precision medicine players plan to ride the resurgence.
After a decade of stagnation, the CNS space is seeing a revival in sales and R&D spending as the market was last year projected to surpass $80 billion for the first time since 2013 and hit around $127 billion.
Recent landmark approvals have brought attention back to the CNS, including the U.S. Food and Drug Administration (FDA)’s greenlight of Eisai/Biogen’s lecanemab (Leqembi) for the treatment of Alzheimer’s disease in 2023, and the FDA approval of Bristol-Myers Squibb’s schizophrenia treatment xanomeline/trospium chloride (Cobenfy) in 2024.
At the same time, Johnson & Johnson’s depression treatment, esketamine (Spravato), is on its way to blockbuster status, showcasing the growth potential of the CNS market.
These successes accompany an emerging shift in psychiatry clinical trials from subjective rating scales to more objective endpoints, including digital and physiological measures, with the potential to better tailor treatments to a patient’s biological makeup.
Startups and scaleups are attracting increasing investor attention for their potential to change the way we treat CNS conditions. Check out our list of the most exciting companies that have netted the biggest investor dollars.
1. Aerska
Founded: 2025 | Headquarters: Dublin, Ireland
Aerska’s name is derived from an Irish proverb stating that people survive in each other’s shelter, emphasising the strength of its team.
This team includes co-founder Jack O’Meara, previously co-founder of the liver-focused RNA interference (RNAi) biotech Ochre Bio, who is driven by the experience of loved ones suffering from Alzheimer’s disease.
Aerska is developing RNAi therapies for neurodegenerative conditions, including Parkinson’s and Alzheimer’s disease.
While there are already FDA-approved RNAi therapies on the market, such as Alnylam’s patisiran (Onpattro), these are typically focused on liver and cardiometabolic conditions rather than the CNS.
Aerska’s technology consists of antibody “brain shuttles” that bind to proteins on the blood-brain barrier (BBB). They then carry a payload RNA into the brain.
The payload, which is designed based on data-driven patient stratification and disease biomarkers, then silences specific genes driving the disease.
Aerska has already raised $60 million since its launch, including a $21 million seed round in October 2025 and a $39 million Series A round in February 2026, co-led by EQT Life Sciences and age1.
The company, which has research operations in the U.K., is using the latest funding to drive its pipeline programs toward clinical testing.
2. Beacon Biosignals
Founded: 2019 | Headquarters: Boston, Massachusetts, U.S.
Beacon Biosignals was co-founded by a team including its CEO—MIT neuroscientist Jacob Donoghue, MD, PhD—and its CTO, the machine learning researcher Jarrett Revels.
Boasting more than 100 employees, the company’s goal is to provide objective biomarkers in drug development that neurology and psychiatry have traditionally lacked compared with other areas of precision medicine.
Its FDA-cleared Waveband device measures the brain’s activity, known as electroencephalography (EEG), while patients sleep at home. The EEG data is then stored, quality-controlled, and fed into AI models that can guide the design of clinical trials.
For example, Beacon’s EEG data can identify patients with Alzheimer’s disease who have worse outcomes and might need a more targeted treatment or a different clinical trial than other patients.
Beacon raised $27 million in a Series A round in 2021 and an oversubscribed Series B round worth $86 million in November 2025.
The B round, which included investors such as Innoviva, Google Ventures, and Nexus NeuroTech, will help the startup to accelerate the discovery of neurobiomarkers and broaden clinical adoption of the technology.
Beacon acquired the French sleep monitoring company Dreem in 2023 to access its monitoring data and headband technology. Beacon then acquired the Ohio-based CleveMed in April 2025 to harness technology measuring breathing, oxygen, and other signals.
3. Brainomix
Founded: 2010 | Headquarters: Oxford, U.K.
Brainomix was founded by a team including CEO Michalis Papadakis, PhD, who was scientific director of the preclinical stroke lab at the University of Oxford.
Brainomix is dedicated to speeding up patient care in cases of stroke, where speedy treatment is key.
Brainomix’s flagship product, Brainomix 360 Stroke, is designed to harness AI to interpret brain scans and detect blood clots in patients with stroke, speeding up clinical decision-making.
The product involves a group of tools that automatically analyze images, including results from computed tomography (CT), CT angiography, magnetic resonance imaging (MRI), and CT perfusion.
Brainomix’s technology doubled the rate of thrombectomy treatment in patients with stroke and reduced hospital triage and transfer delays, according to a 2025 study.
The University of Oxford spinout is at a commercial stage, with operations in more than 20 countries, and is expanding into the U.S.
Brainomix raised a $21.2 million Series B round in 2021 and extended its Series C round from $6.5 million in March 2025 to $25.4 million in February 2026, with leading investors including Parkwalk Advisors and Hostplus. The proceeds will fuel the company’s expansion into the U.S. market.
Brainomix has also partnered with heavyweights, including Nvidia, Boehringer Ingelheim, Medtronic, and GE Healthcare.
Brainomix also has a product dedicated to disease monitoring in pulmonary fibrosis.
4. Circular Genomics
Founded: 2021 | Headquarters: San Diego, California, U.S.
Circular Genomics was spun out of the University of New Mexico, with its founders including CSO Nikolaos Mellios, PhD, and Alexander Hafez, PhD.
The company later moved its headquarters from Albuquerque to San Diego in March 2025 to access scientific and operational know-how from Eli Lilly at Lilly Gateway Labs.
Circular Genomics aims to equip medical professionals with a blood test to detect CNS conditions early, in addition to stratifying and guiding the treatment of patients.
Its technology involves using a polymerase chain reaction (PCR) test of a patient’s blood sample to screen for specific circular RNA molecules produced in the brain that can cross into the blood and be measured as a biomarker of disease in the CNS.
Commercially launched in 2024, Circular Genomics’ MindLight SSRI Antidepressant Response Test predicts whether a patient will benefit from common antidepressants called SSRIs with around 77% accuracy. This is designed to predict a patient’s most suitable antidepressants without needing months of trial-and-error approaches.
The company is applying its technology in Alzheimer’s disease, where the approvals of disease-modifying therapies such as Leqembi have led to demand for tests that can detect the disease at earlier stages than traditional tests.
Circular Genomics raised $15 million in a Mountain Group Partners-led Series A round in December 2025 to finance the development of its technology and expansion of its technology in Alzheimer’s disease.
The company also has its sights on other CNS conditions, including multiple sclerosis and Parkinson’s disease.
5. Omniscient Neurotechnology
Founded: 2019 | Headquarters: Sydney, Australia
Omniscient (o8t)’s founders include CMO Michael Sughrue, MD, a neurosurgeon aiming to improve anatomy maps for other surgeons, and machine learning expert Stephane Doyen, PhD.
o8t’s FDA-approved product Quicktome involves using a patient’s MRI brain scans and AI models to map out a patient’s brain circuitry. These maps, accessible from an electronic tablet, can guide surgery to minimize the risk of brain damage compared to using a generalized anatomical diagram.
Quicktome is already in use at major hospitals around the world, including major centers in the U.S. Its partners include U.S. surgical support firm META Dynamic and the U.S. medical device innovation center, The Jacobs Institute.
o8t has raised more than $60 million, and bagged $14 million (AUD 20 million) in January 2026 as part of a Series D round targeted to reach $25 million (AUD 36 million). The round was led by Australia’s National Reconstruction Fund (NRFC) and OIF Ventures, with the aim of keeping the company based in Australia.
The funding is earmarked to fuel the development and commercialization of Quicktome, and grow o8t’s Australian workforce by more than 40. The company also has operations in Atlanta, Georgia, U.S.
o8t also plans to expand the technology into high-growth markets, including brain computer interface targeting, stroke and traumatic brain injury.
Jonathan Smith, PhD, is a freelance science journalist based in the U.K. and Spain. He previously worked in Berlin as a reporter and news editor at Labiotech, a website covering the biotech industry. Prior to this, he completed a PhD in behavioral neurobiology at the University of Leicester and freelanced for the U.K. organizations Research Media and Society of Experimental Biology. He has also written for medwireNews, Biopharma Reporter, and Outsourcing Pharma.
In the phase 3 EMN24 IsKia trial, transplant-eligible patients with newly diagnosed multiple myeloma who received isatuximab with carfilzomib, lenalidomide and dexamethasone pretransplant induction and post-transplant consolidation showed higher rates of measurable residual disease negativity after consolidation than patients who received carfilzomib, lenalidomide and dexamethasone.
Neurocrine Biosciences said Monday that it would buy Soleno Therapeutics and its treatment for Prader-Willi syndrome for $2.9 billion.
Neurocrine is paying $53 a share for Soleno, a 34% premium to its closing price on Thursday.
Soleno’s drug, Vykat, was approved in March 2025 to treat hyperphagia in patients with the rare genetic disease. Hyperphagia is one of the defining features of Prader-Willi syndrome, causing relentless hunger and leading patients to overeat. Vykat is the only approved treatment for hyperphagia in Prader-Willi patients.
