Radically different
Nature Medicine, Published online: 10 June 2026; doi:10.1038/s41591-026-04444-0
Announced in this Comment and in collaboration with Nature Medicine is the convening of the Brain Health for Economic Resilience Commission, a global, transdisciplinary effort to define, measure and operationalize brain health and cognitive capacity as foundational drivers of economic resilience.
The number of prescription drug shortages in the U.S. fell by 23% last year, marking the second consecutive year of declines and the lowest level since 2017, according to a new analysis that otherwise found troubling signs about medicines that are in short supply.
For instance, the average drug shortage lasted 5.3 years, exceeding the 4.3 years seen in 2024 and greatly outpacing the average two-year shortage experienced in 2019. Moreover, nearly two-thirds of out-of-stock medicines were in short supply for more than three years, and 39% were unavailable for more than five years.
Meanwhile, the 75 drugs that were in short supply last year spanned 130 therapeutic categories, indicating that shortages affected a wide range of diseases and patient populations, according to the analysis by U.S. Pharmacopeia, an independent organization that develops standards for medicines.
Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) reported encouraging interim results from an early clinical trial that tested a new dual vaccine against Lassa fever and rabies. The study found the vaccine to be safe and induced immune responses against both the Lassa fever and rabies viruses (RB). There are currently no vaccines against Lassa fever on the market.
“This vaccine is designed to protect against two viruses of global health importance,” said study principal investigator Justin Ortiz, MD, MS, professor of medicine at UMSOM and vaccine researcher at CVD. “By combining targets into a single product, it could reduce the need for separate vaccination efforts and streamline delivery in settings where access is limited.”
Ortiz is first and corresponding author of the researchers’ published paper in Nature Medicine, titled “Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial,” in which they said, “If efficacy is confirmed, this combination vaccine could help protect populations from two priority pathogens and have a meaningful public health impact in regions where both diseases remain major threats.”
The World Health Organization has identified Lassa virus (LASV) as a public health threat in western Africa and made Lassa fever a priority disease for research. “Transmission occurs primarily through contact with food or household items contaminated by urine or feces from Mastomys rodents, although person-to-person spread can occur via exposure to bodily fluids or contaminated surfaces,” the investigators noted in their paper. Like Ebola, Lassa virus can trigger severe illness and periodic outbreaks in African nations.
Lassa virus infections occur in 300,000 people every year resulting in 5,000 deaths, according to figures cited by the authors, but these numbers are likely an underestimate due to limited surveillance. The disease is particularly dangerous in pregnancy with over 80% of late-term infections resulting in deaths to the mother or fetus. Additionally, regions where Lassa fever is common, such parts of Western and Sub-Saharan Africa, also have a high burden of rabies, with thousands of deaths annually, a disease that is almost always fatal once symptoms develop. The newly reported first-in-human trial was designed to evaluate the safety and immunogenicity of an adjuvanted inactivated rabies virus expressing the Lassa virus glycoprotein complex (GPC) on the surface of the virus. “Scientists at Thomas Jefferson University developed an inactivated rabies-vectored combination vaccine derived from an attenuated rabies strain, LASSARAB, expressing both the rabies glycoprotein and the LASV (Josiah strain) GPC,” the authors explained. “The RABV platform provides a well-established foundation for a dual-target vaccine.”
For the randomized, controlled trial 54 healthy adult volunteers from the Baltimore area were randomly assigned to receive different doses of LASSARAB, with an adjuvant or a licensed rabies vaccine control. Participants received two vaccine doses 28 days apart. Immune responses were studied through 61 days post-vaccination for an interim analysis. The results indicate that LASSARAB was safe with no serious adverse events (AEs) reported after vaccination. Additionally, the candidate vaccine induced rapid and robust antibody responses against both Lassa and rabies viruses when compared with the control, which only induced an immune response against rabies virus.
The study is ongoing, and vaccine safety and immune responses will be further studied through 394 days post-vaccination. “The final study report will be prepared after study completion and will include serious AEs and AEs of special interest through day 394, protocol-defined exploratory LASV and RABV antibody responses assessed at days 121 and 394, and any additional post hoc analyses, as applicable,” the team stated.
If the results indicate continued elevated immune responses from vaccination, researchers will proceed with more advanced clinical trials. Importantly, this investigational vaccine can be freeze-dried for storage, enabling distribution to areas of the world where it may be difficult to maintain cold chains. Importantly, this investigational vaccine can be freeze-dried for storage, enabling distribution to areas of the world where it may be difficult to maintain cold chains.
“These data support the feasibility of a bivalent rabies-vectored vaccine integrated into routine immunization for regions where cold-chain capacity is limited,” the team added.
“This study highlights CVD’s commitment to tackling diseases of global significance,” commented Stefan Kappe, PhD, director of the Center for Vaccine Development and Global Health and the Myron M. Levine Endowed Professor of Pediatrics. “LASSARAB not only targets diseases of concern but utilizes a platform that could make distribution attainable in the areas of the world that are most affected by these diseases.”
Added UMSOM dean Mark T. Gladwin, MD, “Climate change is causing Lassa fever to extend its reach far beyond its Nigerian and West African origins, putting an estimated 700 million people at risk worldwide. By 2070, the number of countries across Africa that will develop ecological conditions suitable for Lassa virus spread could drastically increase, so a vaccine to prevent this deadly infection is desperately needed.”
Last year, before results were available, the trial was highlighted by Nature Medicine in its 2025 feature, “Eleven clinical trials that will shape medicine in 2026,” which identified studies to watch based on their potential to address major unmet health needs.
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Incyte has agreed to acquire Vega Therapeutics for up to $2 billion, the companies said, in a deal designed to bolster the buyer’s hematology pipeline with antibody assets led by VGA039, a Phase III candidate for von Willebrand disease (VWD).
Vega, a wholly owned subsidiary of privately held Star Therapeutics, focuses on developing treatments for bleeding disorders. Vega’s lead candidate VGA039 could, if approved, be the first subcutaneous prophylactic therapy with a more convenient once-monthly, self-administered dosing regimen for patients with VWD, compared with current therapies requiring more frequent (2-3x/week) intravenous infusions.
VGA039 is a monoclonal antibody designed to modulate Protein S with the aim of improving hemostasis, potentially improving the body’s ability to control bleeding in numerous bleeding disorders. VGA039 is under study in the Phase III VIVID-6 trial (NCT07115004), a global single arm crossover study designed to investigate the safety and efficacy of subcutaneous administration of VGA039 as prophylaxis for bleeding in patients with every type of VWD, including those with a high disease burden.
VIVID-6’s estimated completion date is October 2028, with data expected to be read out in early 2029.
“VGA039 fits directly into our strategy of building a top-tier growth company for the future,” Incyte CEO Bill Meury said in a statement. “It is a first-in-class, Phase III asset with compelling early data, a manageable development path and the potential to become an important new growth driver in one of our core therapeutic areas, hematology. The transaction has all of the attributes we look for in business development opportunities.”
In a presentation to analysts Monday morning, Incyte quantified that potential market opportunity as “$1B+ global net sales opportunity.”—an estimate with which three analysts concur:
“VGA039 has the potential to address a clear unmet need for a practical, targeted therapy for von Willebrand disease, and even with conservative assumptions around pricing and market penetration, VGA039 has a clear path to a more than $1 billion market opportunity,” Matt Phipps, PhD, partner and group head of biotechnology equity research with William Blair, wrote Monday in a research note.
“Overall, we believe the deal for VGA039 fits well into Incyte’s current hematology franchise and capabilities and offers a relatively de-risked Phase III asset with blockbuster commercial potential in the 2030s,” Phipps added.
Jessica Fye, a managing director and senior equity research analyst with J.P. Morgan, was also bullish on VGA039’s commercial potential: “We think mgmt [management] framing VGA039 as a potential $1bn+ global sales opportunity is credible and think it should be able to leverage some of INCY’s existing presence with hematology centers.”
Faisal Khurshid, equity analyst with Jefferies, agreed that VGA039 “could have blockbuster potential” assuming it is priced at about $500,000/year compared with the $0.5 to $1 million range of current prophylactic therapies, and assuming ~2,000 patients at hemophilia treatment centers receive frequent IV prophylaxis out of 7,000-10,000 patients who have severe or recurrent bleeds.
“We feel that VGA039 largely fits INCY’s strategic goals and is well-positioned to succeed in Ph[ase III],” Khurshid wrote in a research note.
Despite the positive comments from analysts, Incyte shares dipped 1.7% Monday, from $102.38 to $100.64, though the stock rebounded Tuesday in early trading, rising nearly 3% to $103.31 as of 10:25 a.m. ET.
VGA039 has received the FDA’s Fast Track, Orphan Drug, Breakthrough Therapy, and Rare Pediatric Disease (RPD) designations. The RPD designation made Star Therapeutics eligible to receive a Rare Pediatric Disease Priority Review Voucher (PRV) upon approval of a Biologics License Application for VGA039—eligibility that would transfer to Incyte if its acquisition of Vega occurs as planned. The voucher may be redeemed to obtain priority review for a subsequent marketing application or transferred or sold to another sponsor.
The Breakthrough Therapy designation was supported by interim data from the Phase I/II multidose study (NCT05776069) of VGA039 in adult and adolescent patients with VWD, showing substantial bleed reductions across all types of VWD and all types of bleeds. The data was presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in December 2025.
Vega’s pipeline includes two other programs, both preclinical—a complement therapy program, and an undisclosed program.
Acquiring Vega and its pipeline is among moves Incyte has undertaken in recent months under Meury to recoup the billions of dollars in sales that it stands to lose once its aging blockbuster Jakafi® (ruxolitinib) loses patent exclusivity in 2028—one of the Top 20 Drugs Heading for the Patent Cliff through 2029, according to a recent GEN A-List.
Jakafi, marketed outside the U.S, as Jakavi®, generated $3.093 billion in net product revenues last year, up 11% from $2.792 billion in 2024. Jakafi finished the first quarter with $757.755 million in net product revenues, up 7% from $709,412 in Q1 2025.
Incyte has agreed to pay Star $1.25 billion upfront for Vega, plus up to $750 million in payments tied to achieving sales milestones.
The boards of Incyte and Star have approved the acquisition deal, through which Incyte will acquire all of Vega’s outstanding shares through a stock purchase agreement. The deal is subject to expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions.
Incyte expects to incur an R&D charge of approximately $1.25 billion, to be included in third quarter and full year 2026 GAAP and non-GAAP results, as a result of the acquisition.
However, the benefits of an acquisition by Incyte outweigh its costs, Vega and parent Star Therapeutics reason.
“This milestone reflects our team’s deep commitment to innovation and underscores our strategy to develop first-in-class and best-in-class therapies for serious conditions with high unmet need,” stated Adam Rosenthal, PhD, Star’s founder and CEO.
The post Incyte to Acquire Vega Therapeutics for Up-to-$2B, Growing Hematology Pipeline with Phase III VWD Candidate appeared first on GEN – Genetic Engineering and Biotechnology News.
Spain-based CDMO VIVEbiotech added its 15th in vivo lentiviral vector-based therapeutic program using its platform. These programs, several of which have already received regulatory clearance for clinical trials, including from the FDA, span a range of applications such as in vivo CAR T, rare diseases, gene editing, and vaccines, according to the company.
Growing interest in in vivo cell and gene therapies is driving significant investment, given their potential to address some of the manufacturing and commercialization challenges associated with current ex vivo approaches. However, the direct administration of lentiviral vectors imposes significantly more stringent requirements on the quality attributes of the final product, notes Jon Alberdi, CEO of VIVEbiotech. Accordingly, process control must be optimized to improve both yield and purity. As manufacturing becomes increasingly complex, the scope of analytical characterization is also expanding.
“In vivo lentiviral vectors have the potential to transform treatment paradigms through faster administration and direct therapeutic delivery,” says Alberdi. “However, these advantages come with more stringent manufacturing requirements—from achieving the required purity profile to ensuring consistent performance at scale.”
“As interest in in vivo delivery continues to grow, we are witnessing a fundamental shift in how gene therapies are developed and brought to patients,” adds Marie Fertin, chief custom solution and process development officer at VIVEbiotech. “Our continued investment in capabilities reflects both our confidence in this field and our commitment to enabling our partners.”
The company’s platform has been specifically designed to preserve lentiviral vector integrity throughout the manufacturing process by minimizing shear stress and maintaining cell health, thereby ensuring high vector functionality, continues Fertin. By integrating process intensification strategies with optimized transfection conditions, reduced reagent usage, and improved productivity, the upstream setup contributes to enhanced yields and a significant reduction in cost of goods, she maintains.
Beyond manufacturing, VIVEbiotech reports that it has developed a fully customized analytical framework tailored to in vivo lentiviral vectors, specializing in advanced vector characterization, including potency assay development. A full testing panel is proposed following regulatory feedback received for direct in vivo administration.
A company spokesperson points out that VIVEbiotech also supports large-scale manufacturing of in vivo programs. With more than 3,000 sqm of GMP facilities and seven cleanrooms, VIVEbiotech says it works to ensure timely delivery across development stages. An ongoing expansion plan will further increase manufacturing capacity by 2028, supporting the growing demand for in vivo therapies.
The post Fifteenth <i>In Vivo</i> Lentiviral Vector-Based Therapeutic Technology Added to VIVEbiotech’s CGT Platform appeared first on GEN – Genetic Engineering and Biotechnology News.
Research from the University of Toronto shows long-term exposure to moderate air pollution increases a person’s risk of fatty build up in the blood vessels of the heart, which can lead to serious cardiovascular events like heart attack.
As reported in the journal Radiology, the study also showed that women were particularly badly affected and had an 81% increased risk for obstructive coronary artery disease if exposed to long-term air pollution.
“Even at exposure levels below current Canadian air quality standards, long-term air pollution was independently associated with more advanced coronary artery disease—suggesting current regulations may not be fully protective and that air pollution belongs alongside blood pressure, cholesterol and smoking as a modifiable cardiovascular risk factor,” said lead author Kate Hanneman, MD, associate professor at the University of Toronto, in a press statement.
The study included 11,128 people who underwent cardiac computed tomography (CT) scans who also had available data for air pollution exposure for around 10 years. The average age was 60 years and 52% were men.
In the cohort, median 10‑year exposures were 7.5 μg/m³ for PM2.5, a common measure of particulate air pollution and 13.4 ppb for nitrogen dioxide. These levels are relatively low compared with many historical and low‑/middle‑income settings but still above the latest World Health Organization guideline of 5 μg/m³ for PM2.5 and 5.3 ppb for nitrogen dioxide.
For each addition increment of PM2.5 (1 μg/m³) people in the study had had about 11% more calcium in their coronary arteries and 13% higher odds of having more atherosclerotic plaque. For each increment of nitrogen dioxide (1 ppb) small but measurable increases in calcium (aprx 1%) and plaque (about 4%) were seen in the coronary arteries of those exposed.
After taking into account age, risk factors, medicines, and other differences, each increment higher long‑term air pollution was linked to more severe, artery‑narrowing heart disease in women, but not in men. Each increment increase in PM2.5 was associated with an 80% higher chance of women having a dangerously narrowed coronary artery and each increase in nitrogen dioxide a 6% increased chance.
There was a similar trend in men, but it was not statistically significant after correcting for possible confounding factors.
“These findings add to the growing body of evidence identifying air pollution as a modifiable risk factor for atherosclerosis,” conclude the authors.
“Considering the epidemiologic data linking air pollution to cardiovascular events, these results reinforce the urgency of global public health initiatives aimed at improving air quality to reduce cardiovascular risk.”
The post Exposure to Moderate Air Pollution Raises Cardiovascular Disease Risk appeared first on Inside Precision Medicine.
A highly anticipated Phase III clinical trial has delivered mixed results in testing whether a blood-based test for minimal residual disease (MRD) could guide early treatment for colorectal cancer recurrence (CRC).
Published in Nature Medicine, the randomized double-blind ALTAIR trial tested whether trifluridine/tipiracil (FTD/TPI) could improve outcomes in patients with resected stage I–IV CRC who tested positive for Natera’s Signatera circulating tumor DNA (ctDNA) test after completing standard therapy but had no radiographic evidence of disease. However, the Phase III study—a collaboration between Natera and several Japanese research institutions and hospitals—failed to meet its primary endpoint for investigator-assessed disease-free survival (DFS).
The findings represent the first completed randomized Phase III “treat-on-molecular-recurrence” (TOMR) trial in CRC and underscore both the promise and limitations of ctDNA-guided intervention strategies, highlighting both the promise and limitations of precision oncology.
In the ALTAIR trail, researchers from the National Cancer Center Hospital East in Kashiwa, Kansai Medical University in Osaka, and NHO Osaka National Hospital evaluated a small subset of patients from a larger clinical trial called the CIRCULATE-Japan GALAXY study. Between June 2020 and June 2023, the GALAXY study enrolled 5,514 patients with resectable stage 0–IV CRC across 152 centers in Japan and Taiwan. The GALAXY cohort and other datasets have consistently shown that postoperative ctDNA positivity is associated with markedly increased recurrence risk. ALTAIR addressed the next critical question: whether intervening at the point of molecular relapse alters clinical outcomes.
Among the 1,104 patients who tested positive for ctDNA following surgery in the GALAXY study, 243 were included in the ALTAIR trial, where they were randomly assigned to either six months of FTD/TPI or a placebo. With a median DFS of 9.3 months in the FTD/TPI arm compared to 5.5 months with a placebo, there was a 21% decrease in the risk of recurrence (HR 0.79; 95% CI 0.60–1.05). The difference did not, however, reach statistical significance (P=0.107).
Although the primary endpoint was formally negative, several exploratory analyses suggested biologic activity. Six-month DFS was 70.5% with FTD/TPI versus 45.5% with placebo, indicating an early separation of the survival curves. The benefit, however, decreased over time, with recurrence curves converging by around 24 months—a trend that aligns more with delayed recurrence than with the lasting elimination of residual disease.
The strongest signal emerged in patients with resected oligometastatic stage IV disease. In this subgroup, FTD/TPI reduced the risk of recurrence or death by 47% (HR 0.53; P=0.012). Investigators noted that stage IV patients also had the highest baseline ctDNA burden, suggesting that molecular tumor load may influence responsiveness to MRD-directed therapy.
A post hoc blinded central radiology review also shifted the primary analysis into nominal statistical significance. After adjudication of discordant imaging events, median DFS was 9.2 months with FTD/TPI versus 5.5 months with placebo (HR 0.75; P=0.0406). However, because the analysis was exploratory and non-prespecified, investigators emphasized that it does not alter the trial’s formally negative outcome.
The ctDNA dynamics themselves proved highly prognostic. Patients achieving sustained ctDNA clearance had dramatically superior outcomes compared with those with transient or persistent positivity. In patients with sustained clearance, median DFS was not reached, while it was 11.8 months for those with transient clearance and only 4.4 months for patients with persistently detectable ctDNA.
Notably, spontaneous or transient ctDNA clearance occurred in a subset of placebo-treated patients, highlighting an emerging challenge in MRD-directed oncology: distinguishing biologically meaningful ctDNA positivity from low-level fluctuation or transient shedding.
The study also raises important questions regarding treatment intensity in asymptomatic patients with molecular relapse alone. Toxicity with FTD/TPI was substantial. Grade ≥3 adverse events occurred in 73% of treated patients versus 3.3% with placebo, driven primarily by hematologic toxicity. Severe neutropenia occurred in 56.6% of patients receiving FTD/TPI, and more than one-third required dose reductions. Despite these toxicities, no treatment-related deaths or new safety signals were observed.
The ALTAIR data arrive amid broader uncertainty regarding ctDNA-guided treatment escalation in CRC. The recent DYNAMIC-III trial similarly failed to demonstrate improved recurrence-free survival with ctDNA-guided intensification in stage III disease. Together, the studies suggest that while ctDNA robustly identifies high-risk patients, translating that prognostic information into effective therapeutic intervention remains challenging.
Still, the investigators argue that ALTAIR establishes the feasibility of large-scale MRD-directed trials and provides a framework for future studies using more active regimens, including immunotherapy combinations or anti-angiogenic strategies.
For now, the trial reinforces a central emerging reality in precision oncology: detecting molecular recurrence is increasingly possible. Preventing clinical relapse after detection remains the more difficult task.
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As demand on National Health Service (NHS) U.K. pathology services continues to rise, the shift toward digital pathology has never been more critical. While the NHS 10 Year Plan identifies it as one of the system’s most transformative enablers, digital pathology adoption remains uneven. Damian Doherty, Editor in Chief of Inside Precision Medicine, sat down with Olga Colgan, PhD, strategic marketing director at Leica Biosystems, and Darren Treanor, MB BCh, PhD, consultant histopathologist at Leeds Teaching Hospitals NHS Trust, to explore the pressures facing today’s pathology departments, the transformative potential of digital workflows, and how collaborative partnerships are helping accelerate progress and unlock the full value of digital diagnostics.
Q: The NHS 10 Year Health Plan identifies digital pathology as one of three fundamental shifts, yet adoption remains limited. What are the key barriers?
Olga Colgan: Many pathology departments today are already stretched thin by managing growing workloads, which can make it difficult to pause and do a thorough workflow examination and consider process improvements. Transitioning to digital pathology requires an investment and openness to change. For decades, pathology has been optimized for glass slide review under a microscope, so moving to digital is not just a technology upgrade, but a cultural shift for laboratory staff and clinicians who value the familiarity and comfort of traditional methods.
Proper capital allocation and investment are critical to unlock the benefits of digital pathology. For example, information technology (IT) infrastructure must be capable of supporting high-resolution imaging, secure storage, and rapid sharing of thousands of slides. Regulatory needs must also be considered, as each lab must validate digital workflows to ensure appropriate compliance.
While these upfront hurdles can seem daunting, they lead to significant long-term gains. Digital workflows enable faster slide sharing, improve access to subspecialists, and ultimately improve turnaround times—delivering real benefits for both laboratory teams and patients eagerly waiting for critical results.
Q: What are the key benefits of digital pathology that make it such a crucial step for modernizing NHS pathology services—particularly in terms of workflow efficiency, diagnostic accuracy, and collaborative decision-making?
Colgan: Digital pathology is the quintessential modernization of a pathology laboratory, driving efficiencies in workflows, accuracy, and collaboration. Centralized digital storage provides instant access to prior cases and supports predictive analytics. Eliminating physical slides from the workflow after scanning reduces breakage risks and concerns, misidentification risks, along with space and storage needs.
Beyond efficiency gains, digital pathology unleashes the power of remote collaboration. The ability to share whole-slide images instantly means pathologists can quickly leverage remote expertise within their network, or obtain second opinions in minutes rather than days, accelerating diagnostic confidence and treatment decisions. It also extends expertise beyond geographic boundaries, removing the “postcode-lottery” and providing a basis for equity in pathology diagnostics. This enables rural or underserved regions to access pathologists without the delays, costs, and concerns of physical slide transport. This connectivity transforms pathology into a truly networked resource, ensuring that expertise is available whenever and wherever it’s needed, even after hours.
Further, although in the early stages of routine usage, artificial intelligence (AI) models can add another layer of support by bringing greater quantification and reproducibility to slide analysis, highlighting subtle patterns or abnormalities that may be difficult to identify by eye. Effectively, AI can act as a second set of eyes to further build diagnostic confidence and augment—rather than replace—pathologist review.
Q: How are companies like Leica Biosystems supporting NHS trusts in overcoming digital pathology adoption challenges?
Colgan: It starts with listening. We understand that every laboratory and every pathology department has unique workflows, bottlenecks, and priorities, so our first step is a conversation and analysis to identify those needs and design a tailored roadmap for transformation. This isn’t just about technology; it’s about creating solutions that make the pathology workloads more sustainable, especially at a time when the profession faces significant workforce shortages.
Leica Biosystems partners with labs to deliver systems that meet their demands today, while anticipating future growth and scalability. A great example is Leeds Teaching Hospital and the National Pathology Imaging Co-operative. Combined, they make up the largest national integrated digital pathology network in Europe for routine diagnostics—a milestone that demonstrates what’s possible when technology and collaboration come together. The Leeds Guide to Digital Pathology, volume one and volume two, is packed with practical tips and pragmatic approaches to support successful digital pathology adoption.
Q: What influenced Leeds Teaching Hospital to adopt digital pathology, and what transformation have you experienced?
Darren Treanor: We’ve been involved with digital pathology since the very early days of the technology, and it has become the essential foundation of our teaching and research work at the University of Leeds. We had taken a cautious approach to clinical adoption until we were convinced that the technology was ready—both in terms of clinical safety and technical readiness—and we could ensure that it worked and was safe.
We decided that the threshold for adoption for clinical use was reached in 2015, when we established that the clinical safety was acceptable and that the scanners and viewing software were fit for purpose and would not slow us down. Working in partnership with Leica Biosystems, we adopted a phased approach to 100% digital scanning, starting with a “meaningful pilot” with our four breast pathology colleagues. This group was the most pro-digital in the department and, being located in a separate building, had experienced frustrating delays in the delivery of glass slides between the main lab and their offices. They actively pursued us to “go digital.” The pilot with them was critical for us in planning the laboratory and clinical workflow reconfigurations needed to go digital and, importantly, developing a verification and validation process that allowed us to transition from glass to digital slides while maintaining safety. This process became the foundation of the U.K. Royal College of Pathologists guidelines for digital pathology, which have been adopted in many other countries as well.
We then looked toward the further summit of “100% digital” and took a phased approach, starting with immunohistochemistry (IHC). As a separate part of the lab, this activity could be separately digitized. With digital review of IHC being a lower-risk activity clinically, it allowed us to introduce the rest of our over 40 pathology consultants to the idea of diagnosis on a digital image. Once that was completed, we moved in one final big step to 100% digital scanning, reaching that milestone on a summer’s day in 2018.
Q: What lessons can other NHS trusts learn from your digital transformation journey, and what should be considered as they examine their current workflows?
Treanor: Because of our academic background and partnership with Leica Biosystems, we were very keen to share our experiences of going digital and how to do it. Too many deployments would talk of the great success in using whole-slide imaging, but gloss over the challenges and effort involved in getting there.
We wrote the Leeds guides to provide really simple general-purpose assistance to other labs that are new to digital pathology and didn’t have the benefit of in-house expertise yet.
Looking back, being early adopters, we had the unique challenge of being one of the first centers to go fully digital and pave the way at a time when scanners, displays, and software were just good enough, and the combined global experience of digital pathology was low. We have run many workshops to share our experiences, and it has been interesting to see how the field has evolved in recent times and how much easier it is now to go digital. There are far fewer “unknowns” when going digital now, and modern scanners and workflows are significantly better. For example, our current setup has a very smooth transition from H&E [hematoxylin and eosin] stainer to scanner, which saves a lot of time in the lab and removes a major obstacle to lab operation that we had to work around in the early years. In our early workshops, a deployment was often a multi-year project with a lot of uncertainty and need for a lot of preparatory work; nowadays, labs are much more digital-ready, the timelines are much shorter, and success rates are much higher!
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A medication already used to treat type 2 diabetes may substantially reduce the risk of heart failure hospitalization among people who carry inherited genetic variants associated with cardiomyopathy, according to researchers from the Mass General Brigham Heart and Vascular Institute and the Broad Institute of MIT and Harvard. The study, published in Nature Medicine, found that dapagliflozin reduced the risk of heart failure hospitalization by about 80% in patients carrying cardiomyopathy-associated genetic variants, compared with placebo, indicating that genetic testing could help identify people who could benefit from preventive treatments.
“Historically, identifying a genetic variant for cardiomyopathy mostly meant telling a patient they were at high risk and not having a specific preventative therapy to offer. These data show we do have tools to lower risk in these individuals,” said co-lead author Shinwan Kany, MD, a visiting scientist at the Cardiovascular Research Center with Mass General Brigham Heart and Vascular Institute and the Broad Institute.
Previous studies have already shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin can reduce hospitalizations for heart failure in patients with diabetes and cardiovascular risk factors. The current study sought to find out if patients carrying rare pathogenic variants linked to cardiomyopathy might experience even more benefit from the drug.
The research was driven by an increasing body of evidence that inherited cardiomyopathies contribute to heart failure risk and that pathogenic or likely pathogenic variants are present not only in patients with diagnosed disease but also in asymptomatic individuals. The researchers noted that genetic testing is increasingly used in cardiomyopathy care and family screening, but clinician often don’t know how to proceed when identifying a relevant genetic variant in otherwise healthy carriers.
For this study, the team analyzed whole-exome sequencing data from the DECLARE-TIMI 58 trial, a randomized Phase III trial of dapagliflozin in adults with type 2 diabetes and elevated cardiovascular risk. Of the 12,685 participants with genetic sequencing data, the team identified 121 carriers of pathogenic or likely pathogenic variants in high-confidence cardiomyopathy genes.
Analysis of the data showed that the cardiomyopathy variant carriers faced substantially higher risk of heart failure hospitalization when treated with placebo and experienced an eightfold increased risk of heart failure hospitalization.
Over a median follow-up of 4.2 years, 16% of variant carriers receiving placebo were hospitalized for heart failure. Among carriers treated with dapagliflozin, that figure fell to 3%, representing an 82% relative reduction in risk. By comparison, noncarriers experienced a smaller reduction in heart failure hospitalization risk.
The findings were particularly notable among patients who had not yet developed heart failure. About 82% of the variant carriers in the study had no prior history of heart failure at enrollment. Among that group, dapagliflozin reduced the absolute risk of heart failure hospitalization by 12.8%, compared with a reduction of 0.6% among noncarriers.
“Cardiomyopathy variants represent an actionable genotype which can be used to identify patients who derive a larger benefit from dapagliflozin,” said co-lead author Nicholas A. Marston, PhD, a cardiologist at the Brigham and Women’s Hospital. “This is especially relevant for patients without established heart failure, where such treatment may not be otherwise initiated.”
The researchers noted that the findings should be interpreted within the context of a post-hoc analysis and that the number of variant carriers was relatively small. Because all participants had type 2 diabetes and elevated cardiovascular risk, it remains uncertain whether the same degree of benefit would occur in people without diabetes.
Future research will focus on confirming the findings in prospective clinical trials specifically designed to evaluate preventive heart failure therapies in carriers of cardiomyopathy-associated genetic variants.
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Epigenetics is increasingly powering cancer diagnostics and liquid biopsies. These emerging private companies are spurring the market with structural DNA, fragmentomics, and DNA methylation tests.
Our understanding of the role of epigenetics in disease is growing rapidly, driven by rapid advances in sequencing technology and computing.
Epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA expression can interact with genomic changes to cause cancer. Therefore, diagnostics can detect early signs of disease by screening for these epigenetic signals.
Players including Illumina, Agilent Technologies, and Roche Diagnostics are leading the global market for epigenetic diagnostics, which is expected to swell by 15.5% per year from $17 billion in 2024 to $39 billion by 2030.
Growth is being driven by the increasing affordability of genome sequencing; the integration of AI tools in data analysis; growing investments; and soaring demand for liquid biopsies—noninvasive cancer tests based on blood and urine samples.
One of the first diagnostics with an epigenetic component to be approved by the U.S. Food and Drug Administration (FDA) was Exact Sciences’ (now part of Abbott Laboratories) ColoGuard® noninvasive stool test for colorectal cancer in 2014.
Since then, epigenetics diagnostics have already been generating M&A activity, with deals in the space including Cardio Diagnostics of the U.S. going public via a merger with special purpose acquisition company Mana Capital in 2022; the takeover of Ireland’s EpiCapture by compatriot Trinity Biotech in 2024; the 2023 acquisition of Germany’s Epigenomics AG by U.S.-based New Day Diagnostics; and U.S. Agilent’s acquisition of Avida Biomed, also in 2023.
There is also corporate venture interest with giants like Illumina Ventures, the Labcorp Venture Fund, and Lilly Asia Ventures making investments in small startups.
Check out below for our take on the most promising privately-owned players in the epigenetics diagnostics space, based on their investor attraction and market potential.
1. Arima Genomics
Founded: 2015 | Headquarters: Carlsbad, California
Arima Genomics was spun out of UC San Diego and developed research tools to pinpoint the 3D structure of DNA in cells.
However, the company pivoted to cancer diagnostics after its assay discovered vital clues on how to treat a teenage girl with glioblastoma in 2022.
Arima’s Hi-C technology involves locking the DNA structure in place via crosslinking. DNA strands are then cut with enzymes and labeled with a marker called biotin. Arima uses a process called proximity ligation to connect DNA strands that were physically close together into a single strand, and then sequences the resulting molecule.
Last year, Arima launched a lymphoma test that is delivered via the firm’s laboratory testing service, certified by the U.S. Clinical Laboratory Improvement Amendments (CLIA) program. The test is designed to be used to help patient management by discovering gene fusions and rearrangements for 417 genes in different types of lymphoma.
The test helps to fill in the gaps left by the gold standard, fluorescent in situ hybridization, which can be time- and resource-intensive and lead to conflicting results.
Arima raised $22 million in a Series C round led by Illumina Ventures in 2025 and appointed a former venture partner from Illumina Ventures as CEO. The firm is using the proceeds to launch a pipeline of clinical assays in cancer.
Arima also closed a partnership with Fox Chase Cancer Center earlier this year to co-develop diagnostic tests for lymphoma and sarcoma.
2. DELFI Diagnostics
Founded: 2019 | Headquarters: Baltimore, Maryland
DELFI Diagnostics was founded on an “aha” moment at Johns Hopkins University School of Medicine when a group of researchers aimed to overcome the high costs and low sensitivity of traditional liquid biopsies.
The breakthrough involved hunting for the certain way cell-free DNA fragments appear in the blood. Healthy cells and cancer cells package their DNA in different patterns, reflecting changes in the cell’s genomic and epigenomic machinery.
Using this method of “fragmentomics,” DELFI’s technology can tap into orders of magnitude more data than traditional methods.
DELFI’s product FirstLook Lung uses artificial intelligence (AI) and fragmentomics technology to screen a blood sample for signs of lung cancer. It is designed as an adjunct tool to check whether patients are eligible for lung cancer screening, and is regulated under the CLIA program.
The startup’s other product, DELFI-Tumor Fraction (DELFI-TF), allows pharmaceutical companies to track the effectiveness of a cancer therapy based on a sample of less than one milliliter of plasma.
Delfi raised $5.5 million in a seed round when it was founded, with investors including Menlo Ventures and Illumina Ventures.
The startup subsequently raised a $100 million Series A round led by OrbiMed in 2021, a $225 million Series B round led by DFJ Growth in 2022, and a $34 million debt round last year.
3. Element Biosciences
Founded: 2017 | Headquarters: San Diego, California
Element Biosciences was co-founded by three former Illumina employees who dreamed of democratizing access to genomic sequencing.
The company markets devices designed to sequence genetic information at a lower cost and higher performance than traditional next-generation sequencing. These include AVITI
—its flagship benchtop sequencer—and AVITI24, which can simultaneously analyze DNA, RNA, proteins, and phosphorylated proteins.
The company generated $25 million in revenue in 2023, partly driven by orders of AVITI.
The technology, based on a process called Avidite Base Chemistry (ABC), uses a dye-labeled polymer to bind genetic material and produce sequencing data with the need for fewer reagents than traditional sequencing.
Element is working with epigenetics specialists to boost their research offerings, including Dovetail Genomics and biomodal.
The company has also formed collaborations with diagnostics providers to enhance their offerings, including Revvity’s neonatal genetic tests and Medicover Genetics’ tests for hereditary cancers, metabolic and cardiovascular disorders, infertility, and neonatal diseases.
The company plans to market a clinical diagnostics-focused sequencing product called AVITI Dx, with EU approval expected this year in the form of a CE In Vitro Diagnostic (IVD) mark.
Element Biosciences has raised more than $680 million since it was founded, including a $277 million Series D round in 2024. The asset manager, Wellington Management, led the oversubscribed round, with participation from Samsung Electronics, Fidelity, and more.
This year, Element plans to commercialize a benchtop device, called VITARI, that can sequence a whole genome at high quality for just $100.
4. Nucleix
Founded: 2008 | Headquarters: Rehovot, Israel
Nucleix was initially founded to use epigenetics to trace falsified DNA in forensic investigations. Although the technology worked well, the management team decided to pivot to cancer screening.
Nucleix’s kits involve screening for specific cancer-linked DNA methylation patterns using polymerase chain reaction (PCR) tests.
The company also uses machine learning to construct biomarker panels best suited to the application of interest.
Nucleix’s Bladder EpiCheck® urine test is designed to detect the recurrence of bladder tumors based on changes in DNA methylation. It can also be used to support standard diagnostics when detecting bladder cancer in cases where malignancy is suspected.
The test has a CE mark in Europe and FDA 510(k) clearance in the U.S. for bladder cancer recurrence, meaning it can be marketed as substantially equivalent to another device in the U.S. market.
Nucleix is also developing a blood test for detecting lung tumors based on their DNA methylation signatures.
The company raised a $55 million funding round led by RA Capital Management in 2021, with participation from investors including BlackRock and corporate venture firm Lilly Asia Ventures. It followed up with a $22 million extension round in 2022.
In 2024, Nucleix sealed a strategic partnership with A. Menarini Diagnostics, part of the Italian Menarini Group, to bring its Bladder EpiCheck test to the European market.
5. Precede Biosciences
Founded: 2021 | Headquarters: Boston, Massachusetts
Precede was established by a team comprising Dana Farber Cancer Institute researchers and the venture capital firm 5AM Ventures.
Precede is developing blood tests that measure signals of disease based on the genomic and epigenomic characteristics of cell-free DNA shed into the blood by tumors.
For example, the company tracks gene transcription activity and DNA methylation based on as little as one milliliter of plasma. It can then use machine learning to interpret the results and predict the optimal treatment for each patient.
Precede collaborates with drugmakers to harness its technology to inform the development of next-generation radioligand therapies and antibody-drug conjugates, which depend on the knowledge of target expression and pathway activity rather than single genomic alterations.
The research-focused product Precede Bio Insight is designed to track the progress of cancer, with data spanning breast and prostate cancer.
The second product, Precede Bio Dx, also allows clinicians to select patients for clinical trials based on the blood test results.
The company emerged from stealth mode with $57 million in 2023, and followed up with a Series B round worth $83.5 million in January this year to fund the scaling of its technology as it gains commercial traction.
Among the B round’s syndicate were corporate venture investors Labcorp Venture Fund and Lilly Asia Ventures, and existing investor Illumina Ventures.
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.
The post Beyond the Genome: Five Emerging Leaders in Epigenetics Diagnostics appeared first on Inside Precision Medicine.