This week, Revolution Medicines (RevMed) announced positive topline results from its global Phase III trial of RAS-targeting daraxonrasib in metastatic pancreatic ductal adenocarcinoma (PDAC) patients. In RASolute 302, patients on daraxonrasib showed improvements in progression-free survival (PFS) and overall survival (OS) compared with standard of care cytotoxic chemotherapy.
“With these unprecedented results, daraxonrasib has the potential to achieve our goal of bending the mortality curve in pancreatic cancer. Unlike chemotherapy, daraxonrasib is a RAS-targeted medicine that targets RAS in its active ‘ON’ state, shutting down a key signaling pathway that drives aggressive tumor growth. This is especially important in pancreatic cancer, which is among the most RAS-driven cancers, with more than 90% of tumors harboring a RAS mutation that is the driver of the cancer,” Mark A. Goldsmith, MD, PhD, told Inside Precision Medicine. He is chief executive officer and chairman of Revolution Medicines.
Daraxonrasib patients achieved a median OS of 13.2 months versus 6.7 months for chemotherapy. The drug was generally well tolerated, with a manageable safety profile and with no new safety signals.
RAS is the key oncogenic driver of pancreatic cancer. Nearly all RAS mutations occur at KRAS position G12, but RAS mutations in other isoforms and at KRAS positions G13 and Q61 are also observed.
RevMed now intends to submit the drug for approval by regulatory authorities, including the U.S. Food and Drug Administration as part of a future New Drug Application, and for presentation at the 2026 American Society of Clinical Oncology Annual Meeting. Information about current trials of the drug are available at https://revmedclinicaltrials.com/.
“For patients with metastatic pancreatic cancer, new treatment options are urgently needed to increase survival time and improve quality of life,” said Brian M. Wolpin, MD, MPH, professor of medicine at Harvard Medical School, director of the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute, and principal investigator for the RASolute 302 trial. “The widely anticipated results of this study indicate that daraxonrasib provides a clear and highly meaningful step forward for patients with pancreatic cancer who have experienced progression on prior treatment, typically chemotherapy. I believe that this new approach is a very important advance for the field that I expect will be practice-changing for physicians and improve the care for patients with previously treated metastatic pancreatic cancer.”
Pancreatic cancer is the most RAS-addicted of all major cancers, with more than 90% of patients harboring tumors driven by mutations in RAS proteins. These mutations span a range of RAS variants that fuel aggressive tumor behavior. Daraxonrasib, a multi-selective inhibitor of RAS(ON) proteins, is the first investigational agent in a novel class of RAS inhibitors designed to address a diverse and broad spectrum of oncogenic RAS drivers.
The RASolute 302 trial enrolled patients with pancreatic tumors harboring a wide range of RAS variants, including those with RAS G12 mutations (such as G12D, G12V, and G12R), as well as those without an identified RAS mutation. The primary endpoints of the trial were PFS and OS in patients with tumors harboring RAS G12 mutations. Secondary endpoints assessed PFS and OS in all enrolled patients (the intent-to-treat population), including those with tumors with and without (wild type) an identified RAS mutation.
Daraxonrasib is an oral RAS(ON) multi-selective, non-covalent inhibitor. Cancers driven by a broad range of common RAS mutations include PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. The drug is currently being evaluated in four global Phase III registrational trials, including three in PDAC and one in NSCLC.
Daraxonrasib works by suppressing RAS signaling through inhibition of the interaction between both wild-type and mutant RAS(ON) proteins and their downstream effectors.
Pancreatic cancer is one of the deadliest malignancies, because of its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. In the U.S., recent estimates indicate that each year approximately 60,000 people will be diagnosed with pancreatic cancer, and about 50,000 people will die from it.
Fujifilm Biotechnologies, a CDMO, celebrated the opening of its new, 2,000‑square‑meter quality control (QC) laboratory at its Hillerød, Denmark, commercial‑scale manufacturing site. The expanded QC footprint will enable bioassay and virology operations and support the site’s planned expansion, according to the company.
The laboratory features ventilation systems, personnel, and material airlocks, and an open‑plan layout. The space supports approximately 100 quality team members to conduct viral safety testing for drug substance/product release, scale capacity for complex cell‑based potency and ELISA methods, and perform raw material and critical total organic carbon cleanability studies to accelerate future partner campaigns.
The QC laboratory also incorporates robotics and an ongoing LIMS implementation across the company’s global network of sites to enable digital harmonization and data integrity.
The company doubled its Hillerød capacity in 2024 from six to 12 x 20,000 L mammalian cell culture bioreactors, increasing the complexity and volume for QC testing. The expanded production scale required expanded QC capabilities and advanced analytical equipment to support current operations and anticipated future demand. The QC lab is housed within a new 7,600-square-meter building that also features employee amenities, office and collaboration space, utility services, and an emergency generator to ensure uninterrupted operations and timely delivery of critical test results.
Construction of the lab was completed in last month and subsequently received approval from the Danish Medicines Agency (DKMA) following an on‑site inspection. Laboratory operations will begin in May 2026.
The new QC laboratory is part of Fujifilm Biotechnologies’ kojoX modular, connected network of manufacturing facilities, where harmonized equipment, layouts, methods, and digital systems are used to enable cross‑site workflows and consistent application of quality standards across regions, explains Christian Houborg, senior vice president and Hillerød site lead.
“Today, we are opening a world-class GMP-approved QC laboratory to elevate our quality control and be ready for the upcoming expansion, thereby continuing to manufacture advanced biological treatments for patients with severe diseases, such as cancer and rare autoimmune diseases. Together, we’re making a measurable impact for patients and partners around the world,” he said.
Background: Mobile apps and biofeedback using motion analysis have both been used separately to increase compliance with exercise programs. We developed a mobile app, Osteoarthritis-Rehabilitation Assistant (O-RA), that uses motion analysis technology in the mobile app to assist older adults with performing a knee exercise program. Objective: This study aimed to evaluate the effects of the O-RA app on the compliance and correctness of the exercise program by older adults. Methods: We conducted an assessor-blind, parallel-design, randomized controlled trial with 40 older adults (aged 60 years or older) who had no symptoms and no diagnosis of knee osteoarthritis. Participants were divided into 2 groups: O-RA app (intervention) group and standard treatment (control) group. Both groups were taught 4 types of exercise programs by a physical therapist for 15 minutes and were instructed to do exercises at home every day for 1 week. The number of exercises, the percentage between observed and prescribed exercises, the correctness of exercises, and overall pain during the program were assessed in both groups. Results: The control group had significantly higher compliance with the exercise program than the intervention group (=3.5044, =.001). There was no statistically significant difference in the correctness of the exercise program between the intervention and control groups. The difficulty of use and satisfaction were 47 and 59, respectively, out of the full score of 100. The main problems were the instability and the difficulty using the app. Conclusions: In older adults without knee osteoarthritis symptoms or diagnosis, the O-RA app was not a facilitator but a barrier to the lower extremity exercise program. An updated version, aiming to increase the stability and make it more user-friendly, should be developed; however, more comprehensive data, including qualitative user feedback and standardized usability metrics, will be needed to effectively guide its design. Trial Registration: Thai Clinical Trial Record TCTR20240923002; https://www.thaiclinicaltrials.org/export/pdf/TCTR20240923002
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Background: Large language models use machine learning to produce natural language. These models have a range of potential applications in health care, such as patient education and diagnosis. However, evaluations of large language models in health care are still scarce. Objective: This study aimed to (1) evaluate the accuracy and efficiency of automated fact-checking by 2 large language models and (2) illustrate a process through which a large language model might support a patient in redrafting a prompt to include key information needed for patient safety. Methods: A parallel comparison of 2 large language models and 3 human experts was conducted. A clinical scenario was devised in which a woman aged 23 years questions the safety of retinoid treatment for acne by sending prompts to 2 large language models (GPT-4o and OpenBioLLM-70B). GPT-4o and OpenBioLLM-70B were asked to suggest improvements to the patient’s initial prompt to elicit key information for clinical decision-making. After the patient sent the revised prompt to the large language models, the models were then asked to fact-check the final response. To test the generalizability of automated fact-checking, a set of 20 clinical statements on disparate topics, mostly related to drug indications, contraindications, and side effects, was developed. The large language models also fact-checked these 20 medical statements. The results were compared against the evaluations of 3 clinical experts. The outcome measures were as follows: (1) percentage of accuracy of automated fact-checking, (2) time to complete fact-checking, and (3) a binary outcome for prompt redrafting (advising the patient to revise her prompt by naming her acne medication to address safety concerns). Results: For the scenario of a patient with acne, GPT-4o and OpenBioLLM-70B both had 86% agreement with the clinical experts’ fact-checking. The large language models did not consistently convey the urgency of discontinuing isotretinoin treatment when pregnancy is suspected. In addition, the models did not adequately convey the importance of folic acid supplementation during pregnancy. For the set of 20 medical claims, GPT-4o fact-checking had 100% agreement with that of human experts, whereas OpenBioLLM-70B had 95% agreement. OpenBioLLM-70B diverged from human experts and GPT-4o on 1 question related to pediatric use of antihistamines. The expert fact-checks took a mean time of 18 (SD 3.74) minutes, GPT-4o took 42 seconds, and OpenBioLLM-70B took 33 minutes. The GPT-4o responses for the acne scenario had some inconsistencies but zero fabrication and no obvious omissions. In contrast, OpenBioLLM-70B omitted 1 key information item needed for patient safety. Conclusions: GPT-4o can interact with patients to improve the quality and comprehensiveness of the information contained in health-related prompts. GPT-4o and OpenBioLLM-70B can conduct efficient fact-checking that is close to the level of accuracy of human experts. Human experts need to perform additional checks for accuracy and safety.
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PrecisionLife and Ovation.io have signed a commercialization agreement to bring GLP-1 response genetic tests to the market. Today, the partners announced plans to launch both direct-to-consumer and laboratory developed tests later this year.
The companies had entered a collaboration at the end of last year, leveraging Ovation’s multi-omics and longitudinal clinical data and PrecisionLife’s advanced analytics platform to uncover genetic mechanisms of response to GLP-1 medication. Earlier this year, they reported the identification of a series of biomarker signatures that can quantitatively predict which patients are most likely to respond to GLP-1 therapies and sustain that response over time.
The partners are now actively working on translating this discovery into noninvasive genetic tests for patients to make informed decisions about the likely risks and benefits of these increasingly popular drugs, as well as for drug developers to stratify patients in clinical trials.
“Our teams have generated the world’s most detailed insights into why patients respond differently to these medicines,” said Steve Gardner, chief executive officer of PrecisionLife. “We will make these insights clinically actionable via noninvasive DNA tests supported by our results reporting platform and CLIA lab partners.”
PrecisionLife stressed that their findings go beyond the GLP-1 genetic predictors reported last week by 23andMe. “While that study highlighted a handful of variants associated with modest differences in outcomes, this work identifies combinatorial biomarker signatures that stratify patients and quantitatively predict response—and is already being translated into tests designed for use in real treatment decisions,” a company representative told Inside Precision Medicine.
Over the course of the next six months, PrecisionLife will reproduce, refine, and validate their findings using additional datasets provided by Ovation, including studies to confirm the predicted response to GLP-1 drugs including semaglutide and tirzepatide in a real-world context.
The launch of a consumer DNA test is expected to enable patients to understand their individual safety, efficacy, and tolerability profile for GLP-1 drugs before starting treatment. This could also offer providers a clearer basis for selecting therapies and help payors make more sustainable coverage decisions. The collaborators have stated they will evaluate the opportunity of using these tests to inform reimbursement decisions and expand coverage of certain health plans based on an individual’s predicted response.
For drug developers, laboratory developed tests (LDT) could open up opportunities for more precise patient stratification, improving the probability of success in clinical trials evaluating the expansion of GLP-1 drugs into new indications. The companies are currently in discussions with various stakeholders and sponsors to deploy the LDTs as stratification tools in a clinical setting.
“We’re confident that together we can translate those insights into commercial outcomes and products in GLP-1s and other diseases with huge clinical impact,” said Curt Medeiros, chief executive officer of Ovation.io.
Going forward, the partners will continue to validate their findings and expand the scope of the studies, including identifying additional markers of safety and tolerability to GLP-1 drugs as well as pinpointing further efficacy and safety signals for individual molecules.
The Centers for Medicare and Medicaid Services is proposing to repeal a pathway that currently allows breakthrough devices to qualify for supplementary payments without proving they provide a substantial clinical improvement over alternatives.
Access to lifesaving new technologies can be stymied when hospitals don’t get paid enough to cover their costs. So since 2001, Medicare has given innovative devices a chance at extra payments when they meet three criteria: they’re new and different from what’s currently available, they offer a clinical improvement over existing options, and they’re especially costly.
Since 2021, devices that receive breakthrough designation from the Food and Drug and Administration have gotten an even sweeter deal: In order to qualify for the extra payments, they only have to demonstrate they’re expensive.
For many patients, especially those with chronic or life-threatening diseases, treatment is not a single intervention but a relentless routine.
Cancer patients can spend years tethered to infusion schedules, returning weekly for IV therapies that dictate where they can live, travel, and work. Children with rare metabolic disorders may rely on frequent enzyme infusions, with entire rooms of supplies needed to sustain their care. And for patients in low-resource settings, life-saving biologic drugs often remain out of reach altogether due to cost and infrastructure.
These realities highlight a critical challenge in modern medicine: some of the most potent therapies are the most difficult to deliver, necessitating repeated dosing at centralized locations.
Duracyte, a newly launched biotechnology company, is pioneering a potentially transformative approach to medicine by developing a “living pharmacy” inside the human body. Its core technology, the Hybrid Advanced Molecular Manufacturing Regulator (HAMMR), is an implantable bioreactor designed to produce biologic drugs directly within patients. This innovation could fundamentally change how medicines are manufactured, delivered, and even conceived.
A prototype of Hybrid Advanced Molecular Manufacturing Regulator (HAMMR), a rechargeable implantable device capable of sensing biological signals, monitoring tumor environments and dynamically adjusting therapeutic output in real time. [Rice University]
The founding team combines expertise across bioengineering, medicine, and biotech. Omid Veiseh, PhD, is a Rice University professor and RBL LLC managing partner focused on implantable cell therapies, while Paul Wotton, PhD, is a veteran biotech CEO with deep commercialization experience. Jonathan Rivnay, PhD, of Northwestern specializes in bioelectronics; Robert Langer, ScD, and Daniel Anderson, PhD, are MIT leaders in drug delivery and gene therapy; and Siddharth Krishnan, PhD, of Stanford, contributes expertise in wireless power and implantable devices.
Duracyte is the third venture created by RBL LLC, a Houston-based biotech studio founded by Rice University in 2024. Operating from Helix Park, RBL focuses on rapidly translating breakthrough research into real-world therapies, particularly in areas like oncology and autoimmune disease. Duracyte’s progress is further supported by ARPA-H’s THOR project, a nationwide collaboration aimed at advancing implantable biohybrid therapies from research to clinical application.
Honey, I shrunk the bioreactor
Biologic drugs, including antibodies, hormones, and enzymes, have become a cornerstone of modern medicine. They now represent a substantial share of the pharmaceutical market, treating conditions ranging from cancer to autoimmune diseases. But their production and delivery remain cumbersome.
Traditionally, biologics are manufactured in large-scale industrial bioreactors, purified, stabilized, and shipped to clinics, where they are administered via injection or intravenous infusion. This process is expensive, logistically demanding, and often burdensome for patients, who may require frequent hospital visits over months or years.
Veiseh, a professor of bioengineering at Rice University, has spent much of his career questioning whether this paradigm could be fundamentally reimagined. “What if we could bring this biomanufacturing to the patients and develop implantable bioreactors or injectable bioreactors whereby the biologic could be produced in the body?” Veiseh told Inside Precision Medicine. That question now underpins HAMMR.
At its core, HAMMR is a miniaturized, implantable bioreactor. Roughly the size of a small medical implant, the device houses genetically engineered human cells capable of producing therapeutic proteins. Unlike traditional drug delivery systems, which release pre-manufactured compounds, HAMMR generates biologics inside the patient’s body.
To accomplish this, the device replicates key functions of industrial bioreactors, but in a compact, implantable form. It supplies nutrients and oxygen to the cells, supports their viability, and allows for controlled production of therapeutic molecules.
One of the key technological innovations lies in how HAMMR generates oxygen. Using electrolysis—a well-established chemical engineering process—the device splits water molecules into hydrogen and oxygen. This hybrid oxygenation bioelectronics system for implanted therapy (HOBIT) component provides a steady, localized oxygen supply to sustain the embedded cells. “We’ve got a way to do electrolysis with low power and in a safe manner that actually allows this to be viable for the engineered cells,” Veiseh explained.
Real-time, feedback-controlled medicine
The device also incorporates electronic controls and sensors. Electrical signals can activate or deactivate the cells, effectively turning drug production on or off. Meanwhile, onboard sensors monitor pharmacokinetic and pharmacodynamic data.
This data is transmitted wirelessly to an external interface, enabling clinicians to adjust dosing in real time. Veiseh said, “The implanted device also communicates with an app that allows us to control dosing and get a lot of data from the patient as far as their physiological conditions, meaning the impact the drug is having on the body.”
One of the most transformative aspects of HAMMR is its potential to enable feedback-controlled drug delivery. Rather than administering fixed doses on a set schedule, clinicians could tailor therapy dynamically based on continuous biological data. “For the first time ever, we can create feedback drug delivery systems where you can dose to a pKa level or, better yet, to a pharmacodynamic level, which allows for that precise dosing for every patient,” said Veiseh.
This capability could be especially impactful in oncology, where patients often receive complex combinations of biologics. Current regimens may involve multiple drugs administered on different schedules, requiring frequent clinic visits and careful coordination.
Veiseh described a typical scenario: patients receiving checkpoint inhibitors such as ipilimumab and nivolumab, along with additional biologics like bevacizumab. These therapies often require weekly infusions over extended periods. “The vast majority of patients are getting IV infusions weekly and they are living longer, which is great,” he said. “But now you have patients that are on this regimen for three years.”
HAMMR aims to replace this model with a single implanted device capable of producing multiple drugs, with dosing adjusted digitally rather than through repeated clinical visits. “We’re moving away from physical prescriptions to a world of digital prescriptions,” Veiseh said.
The convergence of components
The idea of implantable bioreactors has been explored for years, but only recently have the necessary technologies matured enough to make it feasible. According to Veiseh, advances in several fields have converged: electronic miniaturization, wireless power transfer, synthetic biology, and biomaterials engineering. Together, these innovations enable the integration of complex functionalities into a small, biocompatible device.
By leveraging established technologies and adapting them for medical use, the team aims to reduce development risk and accelerate regulatory approval.
Wotton, a seasoned biotech executive working with the team, emphasized that many of the underlying components are not entirely new; they are adapted from existing technologies. “One of the advantages here is that these guys have been really intelligent when they’ve taken off-the-shelf technologies,” Wotton told Inside Precision Medicine. “The oxygen technology is lifted from what’s already used in submarines… The battery charging work is being done… The RPE cell lines that we work with… have successfully gotten into the clinic.”
Looking ahead, the team envisions integrating artificial intelligence into the platform. With continuous data collection from implanted devices, machine learning algorithms could identify patterns in treatment response and optimize therapy over time. “You can imagine… this device could now cycle through different therapies, and as it starts seeing efficacy responses, it starts learning,” Veiseh said.
Such a system could enable highly personalized medicine, adapting treatment strategies based on real-time data and accumulated experience across patients.
The HAMMR platform is built around the preparation of polymer-encapsulated cells, obtained from the human immortalized retinal pigment epithelia (RPE) cell line ARPE-19, which has already been used to generate cytokines for treating intraperitoneal tumors with oversight from the U.S. Food and Drug Administration (FDA). This provides a regulatory advantage, as the cells have an established safety profile. These preparations of ARPE-19 cells can be engineered to produce a wide range of biologics beyond cytokines.
A cost-cutting catalog
Veiseh noted that there are more than 300 FDA-approved biologics in the United States, and his team has already created versions of over 150 within this system. “This platform has the potential to really disrupt the biotech market as it exists today,” he said.
The implications extend beyond oncology. Wotton highlighted potential applications in autoimmune diseases, infectious diseases, and metabolic disorders. “There are so many applications of this technology,” he said. “Whether it’s in oncology… or… delivering antibodies like Humira to treat chronic diseases… there are applications where you can treat type two diabetes… HIV.” In each case, the goal is the same: replace repeated injections or infusions with a long-lasting implant that continuously produces therapeutic proteins.
HAMMR could have significant implications for the cost and accessibility of biologic therapies. Biologics are among the most expensive treatments in medicine, with some costing hundreds of thousands of dollars per year. Much of this cost stems from manufacturing, purification, and distribution. By producing drugs directly inside the body, HAMMR could dramatically reduce these costs. “The cost of goods is actually quite low relative to manufacturing today,” Veiseh said. “This is like one-tenth of the price.”
Wotton echoed this point, suggesting that the platform could replace expensive annual treatment regimens with lower-cost implantable devices. “Imagine what you could do if you could replace the $250,000 a year injectable schedule,” Wotton said.
This cost reduction could be particularly impactful in low-resource settings. Veiseh noted that the Gates Foundation has supported the project in part because of its potential to expand access to biologics in developing countries. “Biologics are way too expensive for sub-Saharan Africa,” he said. “But a device that can produce HIV treatments… once yearly… now it becomes… practical for that world too.”
Houston, we have clinical liftoff
Backed by more than a decade of research funding exceeding $100 million from agencies and organizations including DARPA, ARPA-H, the NIH, and the Gates Foundation, Duracyte is preparing to bring its first device into clinical trials. Duracyte plans to initiate a Phase I clinical trial this year evaluating patients with recurrent ovarian cancer. The company has already held multiple meetings with the FDA and completed a pre-IND (Investigational New Drug) meeting. “We have a clear plan as to what it takes to file an IND,” Veiseh said. “We’re on track to actually file… before the end of this year.”
If all goes as planned, the first patients could receive the implant by late this year or early next year. The trial will be conducted in Houston, leveraging partnerships with leading medical institutions, including the renowned MD Anderson Cancer Center. “Our partners at MD Anderson… will be running the first clinical trial,” Wotton said. “Taking advantage of the ecosystem down in Houston.” The proximity of Veiseh’s lab to the clinical site has helped accelerate development, enabling close collaboration between researchers and clinicians.
Despite its promise, the HAMMR platform faces significant challenges. Integrating multiple complex technologies into a single device is inherently difficult, and clinical validation will be critical. Execution risk remains high, particularly in selecting initial indications and navigating regulatory pathways. “We can’t do everything all at once,” Veiseh said. “It’s really thinking about what the value creation is at early stages.”
Prioritization will be key, given the platform’s broad potential. With hundreds of possible biologics and numerous disease targets, choosing the right starting point could determine the company’s trajectory. Wotton emphasized this challenge as well. “What are the challenges we have? Making the right choices with respect to where we go next,” Wotton said.
If successful, HAMMR could mark a fundamental shift in how medicines are delivered and even defined. Instead of prescribing drugs as physical products, physicians could prescribe programmable devices that manufacture therapies on demand. In this model, the distinction between drug and device blurs, giving rise to a new category of therapeutics. “This is so different than what pharma does,” Veiseh said. “I think it’s really interesting to see whether they are also eager to imagine a future of medicine, which gets away from the injectables.”
For now, that future remains speculative. But with clinical trials imminent and a strong foundation of research behind it, Duracyte’s “living pharmacy” is poised to test whether the idea can move from concept to clinical reality.
As Wotton put it, “This is just the tip of the iceberg.”
A randomized Phase II trial offers a rare signal of progress in pancreatic cancer, a disease long marked by therapeutic stagnation, with investigators reporting that the experimental agent elraglusib (9-ING-41) improved survival when added to standard chemotherapy of gemcitabine plus nab-paclitaxel (GnP).
Published in Nature Medicine, the study evaluated the novel drug—developed within an academic setting at Northwestern University—in patients with metastatic pancreatic cancer. The findings suggest that targeting glycogen synthase kinase-3 beta (GSK-3β), a protein not previously exploited clinically in this disease, could open a new therapeutic avenue.
“This is one of the first trials in a randomized setting that has been positive in pancreatic cancer in the last decade,” said Devalingam Mahalingam, MD, PhD, a study leader at Northwestern University. “There was really a barren spell… many failed trials. So it’s nice to see a positive trial.”
A modest but meaningful survival gain
The multicenter trial enrolled 233 patients across North America and Europe, randomly assigning them to receive chemotherapy alone or in combination with elraglusib. Patients receiving the combination lived a median of 10.1 months compared with 7.2 months for chemotherapy alone, and the addition of elraglusib reduced the risk of death by 38%.
Perhaps more striking, survival at one year doubled in the experimental arm (44% vs. 22%), and approximately 13% of patients remained alive at two years—an uncommon outcome in metastatic pancreatic cancer.
Mahalingam emphasized that the benefit was not necessarily reflected in higher tumor response rates. Instead, patients appeared to derive prolonged disease control.
“We didn’t really see much more tumor shrinkage compared to chemo alone,” he said. “But patients stayed on the treatment arm longer… sometimes they would reduce or drop the chemo and just stay on the drug.”
This pattern, he added, points toward a mechanism beyond direct cytotoxicity.
A different mechanism of action
Unlike conventional chemotherapy, which primarily targets rapidly dividing cells, elraglusib appears to act on the tumor microenvironment—the complex ecosystem of immune cells, stromal tissue, and signaling molecules surrounding cancer cells.
The drug inhibits GSK-3β, a protein involved in multiple cellular processes, including metabolism, signaling pathways, and immune regulation. While broadly expressed in normal tissues, GSK-3β can be co-opted by tumors to promote growth and suppress immune responses.
“GSK-3 beta is expressed in many tumors,” Mahalingam said. “It’s part of a central regulator of normal cell functioning… but in cancer, this pathway is used to allow for tumor growth and proliferation.”
Preliminary analyses from the trial suggest that elraglusib may enhance antitumor immunity. Biopsies and blood-based markers indicated changes consistent with immune activation, supporting the hypothesis that the drug helps re-engage the immune system in a tumor type typically resistant to immunotherapy.
“We saw what we call immunomodulatory effects,” Mahalingam noted. “The immune cells might be driving some of the survival benefit we see.”
This is particularly notable given the long-standing failure of checkpoint inhibitors in pancreatic cancer, a tumor characterized by a highly immunosuppressive microenvironment.
Developed in academia
Elraglusib’s development trajectory also sets it apart. The compound originated in academic laboratories more than a decade ago, with early work spanning Northwestern University, the University of Illinois Chicago, and the Mayo Clinic.
“This is what not many drugs are—developed within an academic setting,” Mahalingam said. “It was founded in a chemistry lab… and then moved into a spin-off company to raise funding for trials.”
After preclinical development between 2010 and 2015, the drug entered early-phase trials around 2017 and has since been evaluated across multiple tumor types, with a recent focus on pancreatic cancer.
The randomized Phase II trial marks the first time a GSK-3β inhibitor has demonstrated efficacy beyond early-stage testing.
Broad eligibility, real-world relevance
Investigators designed the study with relatively broad inclusion criteria, enrolling patients with high tumor burden and poor nutritional status—characteristics common in real-world pancreatic cancer populations but often excluded from clinical trials.
“We allowed patients with very large volumes of disease,” Mahalingam said. “We did not restrict patients for albumin… we didn’t engineer the study to look better.”
This approach may partly explain the modest median survival difference, as some patients progressed too quickly to benefit. However, it also strengthens the generalizability of the findings.
Safety and next steps
Side effects associated with elraglusib were generally manageable and consistent with chemotherapy, including hematologic toxicities, fatigue, and reversible vision changes.
The next step will be a confirmatory Phase III trial, with discussions ongoing with regulators.
“We really need to confirm the studies in a large phase three trial,” Mahalingam said, adding that trial design considerations include how to integrate emerging therapies such as KRAS inhibitors.
Investigators are also exploring combination strategies, including pairing elraglusib with immunotherapy or alternative chemotherapy regimens. Early safety studies suggest such combinations are feasible, though efficacy data remain limited.
Potential beyond pancreatic cancer
Given the central role of GSK-3β in multiple cellular pathways, researchers are already investigating the drug’s potential in other malignancies, including hematologic cancers and pediatric tumors such as Ewing sarcoma and medulloblastoma.
“This is a new class of potential cancer therapeutics,” Mahalingam said. “Certainly, there would be excitement in seeing where this target can be applied to other tumors.”
While challenges remain, the trial’s results offer cautious optimism in a field where progress has been incremental at best.
“Even if it means that this class of drugs can be used for future drug development,” Mahalingam said, “it gives an opportunity to expand therapeutic potential—not just for pancreatic cancer, but beyond.”
Background: The integration of artificial intelligence (AI) into clinical practice is contingent on public trust. This trust often depends on physician oversight, yet a significant gap exists between the need for AI-competent physicians and the current state of medical education. While the perspectives of students and experts on this gap are known, the views of the US general public remain largely unquantified. Objective: This study aimed to assess US public perceptions regarding AI in medicine and the corresponding emergent needs for medical education. We specifically sought to quantify public trust in different diagnostic scenarios, concerns about physician overreliance on AI, support for mandatory AI education, and priorities for the future focus of medical training. Methods: We conducted a cross-sectional, web-based survey of adults in the United States in November 2025. Participants (N=524) were recruited via SurveyMonkey Audience. We calculated descriptive statistics, frequencies, proportions (percentages), and 95% CIs for all main survey items. Results: A total of 524 participants completed the survey. Most (n=329, 62.8%; 95% CI 58.6%‐66.9%) placed the most trust in a physician’s diagnosis based on their expertise alone; only 7.8% (n=41; 95% CI 5.5%‐10.1%) trusted an AI-first diagnostic model. Trust was highly contingent on training: 93.9% (n=492) of participants rated formal physician training on AI limitations as “essential” or “very important.” Widespread concern about physician overreliance on AI was reported, with 81.1% (n=425) being “very concerned” or “extremely concerned.” Consequently, 85.1% (n=446) agreed or strongly agreed that training on AI use, ethics, and limitations should be mandatory in medical school. When asked about future educational priorities, 70.2% (n=368; 95% CI 66.3%‐74.1%) believed that medical education should focus on human-centered skills (eg, empathy and communication) over clinical skills. Conclusions: The US public expressed conditional trust in medical AI, strongly preferring physician-led and critically supervised models. These findings reveal a clear public mandate for medical education reform. The public expects future physicians to be mandatorily trained to appraise AI, understand its limitations, and refocus their professional development on the human-centered skills that technology cannot replace.
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Alterations in excitation/inhibition (E/I) balance and changes in motor neurons (MN) activity may contribute to MN vulnerability in ALS. The balance of pathogenic versus adaptive changes occurring in inhibitory synapses and affecting E/I balance remain unclear. Confocal microscopy of MN from P45 male SOD1G93A mice reveal downregulated GlyR but upregulated GABAR clusters at inhibitory synapses. GlyR and GABAR respond to PSAM and DREADD chemogenetic alterations of MN excitability, with increased activity driving increase in inhibitory clusters. An E3 ligase-conjugated intrabody (GFE3) degrades Gephyrin, decreases GABAR and GlyR clusters, increases net activity, and downregulates disease markers. However, simultaneous decrease of inhibition and increased activity by actPSAM and GFE3 shows no net beneficial effects on disease markers. Thus inhibitory synapses are involved in the early phases of ALS pathogenesis and respond to persistent homeostatic loops, and their suppression delivers a net activity increase, offering potential benefits on disease pathways.
