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Bradford Teaching Hospitals uses AI to detect skin cancer faster
Bradford Teaching Hospitals NHS Foundation Trust has begun using AI with the aim of detecting skin cancer earlier.
NHS tech investment needs better delivery, not greater urgency
NHS digital investment is being held back not by lack of urgency but by weak delivery on the ground, writes Professor Joe McDonald
Psilocybin-Induced Brain Changes May Explain Therapeutic Effects
Researchers at University of California, San Francisco and Imperial College London have shown that a single dose of psilocybin, the psychedelic compound found in magic mushrooms, causes likely anatomical brain changes that last for up to a month after the experience.
The study, involving healthy volunteers who had never taken a psychedelic, links temporary shifts in brain “entropy”—which is the diversity of neural activity occurring in the brain—to insight. This suggests the psychedelic trip itself is important to the drug’s longer term therapeutic effects.
The researchers found that a high dose of psilocybin led to increased entropy in the minutes and hours after taking the drug. The degree of entropy predicted how much insight, or emotional self-awareness, the participants felt the next day; and this, in turn, forecasted improvements in their sense of wellbeing a month later.
The findings may help to explain psilocybin’s therapeutic effects on conditions such as depression, anxiety, and addiction. “Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, PhD, the Ralph Metzner distinguished professor of neurology at UCSF. “Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health. It suggests that the trip—and its correlates in the brain—is a key component of how psychedelic therapy works.” Carhart-Harris is senior and corresponding author of the team’s published paper in Nature Communications, titled “Human brain changes after first psilocybin use.”
“Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown,” the authors wrote. Psilocybin is the precursor of the compound psilocin, a serotonin receptor agonist. “Converging evidence supports a role for serotonin 2A receptor (5-HT2AR) agonism in eliciting the characteristic brain and subjective effects of this and related psychedelics in humans,” the team continued.
For their newly reported study, Carhart-Harris and colleagues carried out an exploratory, placebo-controlled, within-patient study in 28 psychedelic-naïve participants who each received a single, high-dose (25 mg) of psilocybin. The researchers used an assortment of brain imaging and brain measurement techniques, some of which were carried out during the peak of the psychedelic experience, as well as before and one-month after drug administration. “This was an exploratory, hypothesis-generating mechanistic study in healthy volunteers,” the authors noted. None of the 28 people in the study had a diagnosed mental health condition, which gave the scientists greater freedom to do more testing.
In the first part of the experiment the subjects were given a 1 mg dose of psilocybin, which the researchers regarded as a placebo, and were then monitored with EEG, which records brain activity from electrodes on the scalp. Over the next few weeks, the researchers measured their subjects’ psychological insight, wellbeing, and cognitive ability. They examined brain activity with functional MRI (fMRI) and brain connectivity with diffusion tensor imaging (DTI).
One month after the placebo, the subjects were given 25 mg of psilocybin, a dose capable of eliciting a strong psychedelic trip. During the experience, researchers again measured the subjects’ brain activity with EEG, and in the following weeks they repeated the same tests they had given after the 1 mg dose.
This enabled the scientists to compare the effects of the psychedelic trip on the brain and mind to the effects of the placebo. “The multimodal neuroimaging design allowed us to observe changes in brain function and (potential) anatomy from 1-h (EEG) to 1-month (DTI) after high-dose psilocybin,” they explained.
The investigators found that within 60 minutes of taking the 25 mg dose of psilocybin, EEG revealed higher entropy, suggesting that the brain was processing a richer body of information under the psychedelic. A month later, the researchers looked at their subjects’ brains using DTI, which measures the diffusion of water along neural tracts in the brain, and found that they were denser and had more integrity. This is the opposite of what happens in aging, which makes these tracts more diffuse.
The researchers cautioned that more work needs to be done to better understand the meaning of this finding, but the result is a never-before-seen sign of how psychedelics can change the brain. ”The inclusion of DTI enabled us to test for long-term changes in the integrity of white matter tracts post psilocybin,” the authors stated. “Results revealed decreased axial diffusivity in prefrontal-subcortical tracts 1-month post 25mg psilocybin.”
The day after the 25 mg dose, all but one of the 28 subjects rated the trip as the “single most” unusual state of consciousness they had ever experienced. The remaining person rated it as among their top five. The study participants said they had experienced more psychological insight after taking the 25 mg of psilocybin than they had after the 1 mg placebo. The subjects also reported increased wellbeing two and four weeks after the study. This was measured from responses to statements such as, “I’ve been feeling optimistic about the future,” and “I’ve been dealing with problems well.”
As the scientists noted in their paper, “A predictive relationship was also found between brain entropy and longer-term mental-health changes—namely, improved wellbeing. Improved wellbeing could be predicted directly from acute increases in brain entropy as early as 1-h post dosing.”
A month after the study the study individuals also scored better on a test of cognitive flexibility. “Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought,” said first author Taylor Lyons, PhD, a research associate at Imperial College London. “The fact that these changes track with insight and improved well‑being is especially exciting.”
The scientists found that the subjects who had experienced the largest increases in brain entropy in the minutes to hours after taking psilocybin were the most likely to have increased insight the next day and increased wellbeing a month later. The researchers concluded that improved wellbeing was driven by the experience of insight.
The authors suggest that the study findings could improve treatment for people with mental illness using psilocybin, for example, by ensuring that the right dosage is used to produce the right amount of brain entropy to promote insight. “We already knew psilocybin could be helpful for treating mental illness,” Carhart-Harris said. “But now we have a much better understanding of how.”
In their paper the team concluded, “The present multi-modal neuroimaging study in healthy participants sheds light on the brain effects of first-time high-dose psychedelic use and the therapeutic action of psilocybin-therapy, suggesting that therapeutically relevant changes—i.e., improved wellbeing—can be forecast via an acute human brain action, i.e., an entropic brain effect, that is well-known to relate to the psychedelic experience … Results support a role for psychological insight in mediating the causal association between the entropic brain effect and potentially enduring improvements in wellbeing.”
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Muscle Quality and Fat Distribution Predict Mortality Risk Better than BMI
Researchers at the University Medical Center Freiburg in Germany, say that detailed measures of body composition derived from whole-body MRI scans can predict diabetes, cardiovascular events, and mortality risk better than current methods that rely on body mass index (BMI). Using MRI imaging data from more than 66,000 people, the team has developed age-, sex-, and height-adjusted reference standards that show how fat and muscle are distributed across the body and how these patterns relate to health outcomes. Their findings, published in the journal Radiology, show analysis of both the quantity and quality of skeletal muscle, along with where fat is distributed in the body, can provide a more accurate way to determine risk as opposed to weight-based methods alone.
“Many risk scores and treatment decisions still rely on BMI or waist circumference because they are simple to obtain,” said senior author Jakob Weiss, MD, PhD, an interventional radiologist at University Medical Center Freiburg. “But BMI does not reliably reflect a person’s actual body composition.” This is one of the central findings of the study: that individuals with similar BMI values can have markedly different distributions of fat and muscle, which carry different levels of risk for cardiometabolic disease and mortality.
The team’s retrospective study analyzed whole-body MRI scans from 66,608 people using data from the UK Biobank and the German National Cohort collected between April 2014 and May 2022. The cohort had a mean age of 57.7 years and an average BMI of 26.2. Using a fully automated deep learning framework, the researchers quantified multiple body composition measures, including subcutaneous adipose tissue, visceral adipose tissue, skeletal muscle, skeletal muscle fat fraction, and intramuscular adipose tissue. These measures were normalized for age, sex, and height. A score is developed from these data to show how far individuals deviated from a population-adjusted reference.
“Whole-body MRI–derived BC (body composition) z-scores were used to identify at-risk individuals and predict cardiometabolic outcomes and mortality beyond traditional risk factors.” They then used the z-score categories to assess associations and clinical outcomes.
Their data showed that individuals with high visceral fat had a 2.26-fold increased risk of developing diabetes. High intramuscular fat was associated with a 1.54-fold increased risk of major adverse cardiovascular events, while low skeletal muscle was linked to a 1.44-fold increase in all-cause mortality.
The deep learning system used to develop the risk profiles was trained and evaluated against radiologist-defined reference standards, allowing it to extract volumetric measurements across the entire body rather than relying on single cross-sectional slices. This method allowed the researchers to capture meaningful variations in muscle quality and fat distribution that are not visible through other techniques.
“Manual BC measurement in large-scale imaging datasets is prohibitively time-consuming,” the researchers wrote. “However, recent advances in deep learning have enabled fully automated, accurate, and efficient quantification from cross-sectional imaging.” This capability allowed the team to construct reference curves reflective of how body composition changes with age and differs between men and women.
Importantly, the research shines a light on the limitations of using BMI to determine future risk. Because BMI is calculated using only two metrics, height and weight, it does not distinguish between fat and muscle or account for where fat is stored. Because of this, two people with the same BMI may have very different levels of visceral fat or muscle mass, factors that can lead to different to different health risks. The researchers showed that deviations in these specific components, captured via their MRI-based z-scores, were predictive of outcomes even after accounting for traditional risk factors.
“It’s not only how much muscle you have, but also it’s the quality of that muscle,” said first author Matthias Jung, MD, a radiologist at University Medical Center Freiburg. “Knowing the volume of intramuscular fat gives us a window into muscle quality that other methods like BMI, bioelectrical impedance analysis, or DEXA can’t easily provide.” This distinction is relevant because intramuscular fat is linked to metabolic dysfunction and cardiovascular risk.
The study also produced a web-based calculator that allows clinicians and researchers to compare individual patient data with population-based reference values. According to Weiss, this tool could be applied to existing imaging studies. “A dedicated whole-body MRI is not necessarily required. If a routine CT or MRI body scan already exists, the information can be extracted for benchmarking against the reference values,” he said.
The study has limitations, including a cohort of primarily White Western European adults, which may impact the generalizability of the findings. The researchers also pointed out that whole-body MRI is not routinely performed in clinical practice, although they provided reference values for commonly imaged regions such as the chest, abdomen, and pelvis to address this.
The team will continue their work by seeking to validate the reference curves in clinical populations and exploring their use in predicting treatment outcomes, including toxicity, survival, and recurrence in cancer patients. The team also plans to develop disease-specific reference values for broader patient groups to broaden the use of body composition analysis into clinical care.
The post Muscle Quality and Fat Distribution Predict Mortality Risk Better than BMI appeared first on Inside Precision Medicine.
TRACS Enables Strain-Level Tracking of Microbial Transmission
Tracking microbes is challenging, particularly when there are coexisting strains of the same species within metagenomic data. However, overcoming that challenge is important for inferring transmission of both pathogenic and commensal microbes.
A new tool, called TRAnsmision Clustering of Strains (TRACS), distinguishes between closely related bacterial strains. The “highly accurate algorithm” can be used for “estimating genetic distances between strains at the level of individual single nucleotide polymorphisms, which is robust to intra-species diversity within the host.”
Researchers used the TRACS tool to map the transmission of SARS-CoV-2, Streptococcus pneumoniae, and Plasmodium falciparum (the causative agent of malaria) across different populations. The tool may play an important role in infection prevention, outbreak response, and the development of treatments designed to help the human microbiome fight infection. They note that this tool can be used across microbial kingdoms to uncover strain dynamics.
“Traditionally, this has been very difficult for us to achieve, yet it is incredibly important to know, as people can carry several slightly different versions or strains of the same species at once, which makes it challenging to understand how microbes move between individuals,” notes Gerry Tonkin-Hill, PhD, group leader at the the Peter MacCallum Cancer Centre and the Peter Doherty Institute at the University of Melbourne, Australia. “Using this new technology, we can now overcome this challenge and gain a clearer picture of how microbes are shared between people. This will give us a better understanding of how microbes spread to help us prevent infection in vulnerable populations, like our cancer patients.”
This work is published in Nature Microbiology in the paper, “Strain-level transmission inference across multi-kingdom metagenomic data using TRACS.”
Being able to track the spread of pathogens using genomics has become a major tool in public health and can help inform new ways to prevent transmission. Additionally, it can help understand more about how lifestyle and environmental factors are involved in the transmission of these pathogens, and their role in the microbiome.
Currently, genomic tools used to track multiple bacterial species do not have the speed and flexibility required for routine public health monitoring and can struggle to distinguish between samples transmitted recently and those transmitted years ago. Furthermore, it can be difficult to continuously add in new samples, making real-time surveillance difficult.
The TRACS algorithm identifies and analyzes Single Nucleotide Polymorphisms (SNPs) to estimate how closely related the pathogens are, and if they are likely to have recently been transmitted. This approach allows for the continuous integration of new samples, making it an ideal tool for accurately identifying transmission networks and ruling out transmission events in ongoing public health applications.
In this new study, the team used TRACS to map pathogen transmission networks across three different populations, all of which had different genomic data. They applied it to SARS-CoV-2 data from U.K. hospitals, deep population sequencing data of Streptococcus pneumoniae and single-cell genome sequencing data from malaria patients infected with Plasmodium falciparum. They found that the tool was able to identify different pathogens in one sample and infer where these were each transmitted.
They also used TRACS to study how microbes are passed from mothers to infants and found that one beneficial bacterium, Bifidobacterium breve, persisted in infants longer than previously recognized, something that previous methods have missed.
More superficially, the authors note that “applying TRACS to gut metagenomic samples from a mother–infant cohort revealed species-specific transmission rates and identified increased the persistence of Bifidobacterium breve in infants, a finding previously missed owing to the presence of multiple strains.”
“This research could support the development of new treatments that use beneficial microbes to improve health,” notes Trevor Lawley, PhD, group leader at the Wellcome Sanger Institute. “By understanding exactly how microbes move between people and which of them are more likely to thrive in their microbiome, we could design better ways to increase helpful gut microbes and investigate whether there are ways to use these to help prevent infections, opening the door to safer healthcare environments and new microbiome-based therapies.”
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Optical Pooled CRISPR Screen Reveals Regulators of NF-κB Dynamics in Human Cells
Tilmann Buerckstuemmer, PhD
CSO
Myllia Biotechnology
Panelist
Tilmann Buerckstuemmer, PhD
Tilmann Buerckstuemmer, PhD, is a CRISPR enthusiast since the early days of CRISPR. Originally trained as a biochemist, he joined Haplogen as principal scientist and later became their CSO. Following the acquisition by Horizon Discovery, Tilmann served as director of research and development and later as head of innovation, where he oversaw the company’s technology platform and innovation agenda. In 2018, he co-founded Myllia Biotechnology which focuses on single-cell CRISPR screens. He is also the CEO of bit.bio discovery, a joined venture between Vienna-based Myllia Biotechnology and Cambridge-based bit.bio. Tilmann is passionate about science and enjoys working with multi-disciplinary and multi-national teams.
Jens Durruthy Durruthy, PhD
Director of Product Management
Element Biosciences
Panelist
Jens Durruthy Durruthy, PhD
Jens Durruthy Durruthy, PhD, is the director of product management at Element Biosciences. Prior experience includes a decade at 10x Genomics, where he developed and oversaw the product portfolio for Chromium products. Jens held the position of LSA Bio/Genomics Fellow at Life Science Angels, conducting extensive research on investment opportunities in biotech and genomics startups, and has worked in various consulting roles, focusing on product development and market analysis. Educational credentials include a PhD in biomedical engineering from Stanford University and a diploma in medical biotechnology from Technische Universität Berlin.
Broadcast Date:
- Time:
Integrated pooled CRISPR screening linked to imaging readouts accelerate target identification and functional characterization of signaling pathways. A good example of this can be found in studies of NF-κB signaling, which is central to inflammatory responses and driven by rapid nuclear translocation of the p50/p65 complex to activate transcriptional programs following cytokine stimulation.
In this GEN webinar, Tilmann Buerckstuemmer, PhD, CSO at Myllia Biotechnology will show how high-throughput pooled CRISPR screening combined with cell painting readouts characterized important signaling pathways using NF-κB nuclear translocation as a case study. During the webinar, you will learn how the AVITI24
platform from Element Biosciences profiled ~440,000 cells in a pooled CRISPR screen targeting 195 genes. Linking genetic perturbations to p65 subcellular localization and cell painting features in a single workflow enabled identification of known pathway components, uncovered regulatory roles for chromatin-modifying complexes, and improved interpretation of phenotypic outcomes using morphological features.
Key takeaways include:
- Strategies for linking CRISPR perturbations to protein localization and morphological features at single-cell resolution
- Identification of hitherto poorly characterized chromatin modifying complexes in regulating NF-κB signaling
- The value of multimodal readouts, including morphology, in adding depth and confidence to recovered biology
- How this approach supports mechanism-of-action studies and enables identification of both positive and negative regulators of signaling pathways
A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.
Produced with support from:
The post Optical Pooled CRISPR Screen Reveals Regulators of NF-κB Dynamics in Human Cells appeared first on GEN – Genetic Engineering and Biotechnology News.
StockWatch: Patient Death, Rival’s Patent Challenge Sink Erasca Shares
Sometimes a patient’s death is enough to send a stock tumbling. Other times, the fear of litigation that often arises whenever a new therapeutic approach emerges can send shares sinking. This past week, Erasca (NASDAQ: ERAS)—whose name is a portmanteau for “erase cancer”—ran into both, causing its share price to nosedive 53%.
The precision oncology company, whose drugs and combination therapies focus on fighting cancer by shutting down the RAS/MAPK pathway, shared preliminary positive albeit early clinical dose escalation data for ERAS-0015, pooled from two Phase I trials. The oral pan-RAS molecular glue is being developed to treat solid tumors that include non-small cell lung cancer (NSCLC) and pancreatic cancer (formally pancreatic ductal adenocarcinoma or PDAC).
ERAS-0015 achieved unconfirmed overall response rates (uORR) of 62% to 75% in KRAS G12X NSCLC patients dosed at 16–32 mg once daily, with the low percentage in second line or greater KRAS G12X NSCLC (37 patients), and the high percentage in post-ICI/platinum (second and third line) KRAS G12X NSCLC (37 patients). In pancreatic cancer, which has an overall five-year survival rate of just 13%, ERAS-0015 achieved unconfirmed overall response rates ranging from 40% to 50% in second-line positive KRAS G12X PDAC.
However, tucked in footnotes on pages 25 and 43 of its investor presentation detailing the positive data was the disclosure that a 66-year-old male patient died after his grade 3 treatment-related adverse event (TRAE) of pneumonitis progressed to grade 5 after supportive care was withdrawn at the patient’s direction. The patient, who had “heavily pretreated” metastatic pancreatic cancer, received 24 mg of ERAS-0015, Erasca said.
“The patient had pulmonary metastases, a history of right lung cryoablation, and no history of lung radiation. The patient presented to the ER approximately a month after starting ERAS-0015 with grade 3 pneumonitis that was treated aggressively with immediate discontinuation of ERAS-0015, high-dose steroids, and infliximab,” Erasca explained. “The patient requested withdrawal of supportive care and ultimately died of the event.”
“Different outcome”
During an April 27 conference call, Jonathan E. Lim, MD, Erasca’s chairman, CEO, and co-founder, told analysts the death was “a very rare event” as pneumonitis is a rare drug-related toxicity seen in many oncology drugs.
“The withdrawal of supportive care is really why this progressed from grade 3 to grade 5,” Lim said. “The investigator told us directly that he thought that if the patient had continued supportive care, then it might have been a different outcome. So yes, it’s very unfortunate for the patient, but that was the feedback.”
Lim added that Erasca hasn’t seen any other grade 4 or grade 5 TRAEs. He told analysts that both FDA-approved KRAS G12C inhibitors have warnings and precautions for pneumonitis in their labels—Lumakras® (sotorasib), marketed by Amgen (NASDAQ: AMGN); and Krazati® (adagrasib), marketed by Bristol Myers Squibb (NYSE: BMY). Lim also cited Revolution Medicine (NASDAQ: RVMD)’s daraxonrasib (formerly RMC-6236), which Erasca is citing as a comparator to ERAS-0015, had also reported pneumonitis at a level of 1 out of 50 patients for monotherapy.
The same day as the data release and patient death disclosure, Erasca also revealed in a regulatory filing that it had received a letter from legal counsel for Revolution, Erasca’s arch-rival developer of RAS inhibitors against cancer. Revolution told Erasca that ERAS-0015 was “substantially equivalent” to compositions claimed by Revolution in its U.S. Patent No. 12,409,225, titled “RAS Inhibitors”, and as a result, Erasca “infringes” the patent.
“The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers,” according to the text of the patent, which lists Revolution as its assignee.
Revolution also contended that Erasca was liable as licensee for ERAS-0015, and that Erasca “improperly” compared preclinical data of ERAS-0015 and daraxonrasib publicly.
No wrongdoing, Erasca insists
Erasca insists it did nothing wrong, stating in the filing that it “intends to contest the allegations vigorously.”
Lim echoed the company’s response in the filing during an interview with GEN, where he stated that the company believes Revolution’s assertions to be without merit.
“We have no reason to believe that ERAS 15 infringes any patent—including RevMed’s accusation, which is based on the doctrine of equivalence, rather than an accusation of direct infringement,” Lim said. “RevMed did not provide details to support its claim that others engaged in trade secret misappropriation, and we have no reason to believe any such thing occurred.”
“In addition, we believe that all of our preclinical data comparisons have been appropriate. And all of our data presented on the R&D Day were not based on head-to-head studies but on cross-trial comparisons. We made that very clear during the presentation,” Lim added.
Through a spokesperson, Revolution told GEN the company was acting to defend its inventions and the IP behind them.
“We are committed to protecting the strong foundation of innovation we have built over more than a decade through transformative science and significant investment,” Revolution stated. “While we do not comment on the specifics of ongoing legal matters, we remain confident in the strength of our intellectual property. Our focus remains on advancing our science to deliver innovative medicines that make a meaningful impact for patients.
Slumping stock
Erasca investors reacted coolly to the patient death and prospect of a legal wrangle with Revolution. Erasca shares slumped 11% from $21.49 to $19.15 the day of the data announcement and regulatory filing. The share price plunged 48% to $9.90 Tuesday and fell another 8% Wednesday to $9.11 before bouncing back 17% to $10.65 Thursday as investors bought the dip, then finished Friday sliding 6%, closing at $10.03.
Despite the selloff, Erasca shares have more than quadrupled over the past six months, rocketing 314% from $2.42 on October 31 and catapulting 573% over the past year (from $1.49 on May 1, 2025).
Revolution shares rose 3% this week. After sliding nearly 3% from $135.30 to $131.67 on April 27, the stock benefited from Erasca’s slump by jumping 10% to $144.83 before fluctuating, closing Friday at $139.48.
“We view the (-)ve [negative] post‑data reaction as overdone, as ERAS‑0015 looks like a formidable competitor in the pan‑RAS landscape,” Maury Raycroft, PhD, equity analyst with Jefferies, wrote in a research note.
Raycroft cited Erasca’s comparing its 62%/75% uORR in NSCLC to the confirmed 38% ORR cited for daraxonrasib in a 2025 study by researchers from Revolution and several clinical partners. Among second and third-line treatment patients post‑ICI/platinum, efficacy appeared broadly consistent across geographies, Raycroft noted, w/ uORR of 71% in the United States (12 patients), where ERAS-0015 was studied in the Phase I AURORAS-1 trial (NCT06983743), and 73% in China (11 patients), where partner Joyo Pharmatech sponsored a trial known as STAR or JYP0015M101 (NCT06895031).
“Early durability is also encouraging, w/ progression observed in 1/27 pts in the China study and 2/12 in the U.S. study; though, follow‑up remains limited (median likely ~3–4 mos), so durability conclusions are premature,” Raycroft cautioned.
In pancreatic cancer, pooled U.S. and Chinese patient data ranged from 40% uORR at 16–32 mg (20 patients), to 42% uORR at 24–32 mg (12 patients), and 50% uORR at 32 mg once daily (two patients).
Expansion doses
“Right now, we think the lower doses at 8 and 16 milligrams, for instance, seem to be relatively underpowered against pancreatic cancer compared to 24 to 32 milligrams. So, based on the totality of efficacy, safety, tolerability, and PK data, we have determined 24 and 32 milligrams to be the recommended doses for expansion,” Lim told GEN. “So we have already begun to expand out those doses to treat patients at both 24 and 32 milligrams.”
All but one of 24 responding NSCLC patients, and 20 out of 23 responding PDAC patients, remain on treatment, including all responders treated at the 24 and 32 mg once daily recommended doses for expansion (RDEs).
Erasca said ERAS-0015 showed clinical potential for combinability with standard-of-care doses of the anti-EGFR monoclonal antibody panitumumab in fighting colorectal cancer (CRC), where EGFR is a key mechanism for acquired resistance. Through the data cutoff date of March 31, Erasca showed no dose-limiting toxicities among three patients, of which one showed an unconfirmed partial response in an efficacy-evaluable patient with metastatic CRC: “That’s really exciting to have,” Lim said.
Compelling opportunities
“For monotherapy, we think lung and pancreatic are compelling opportunities, and then for colorectal cancer, combination therapy will likely be required, so we’re focused on the combination with EGFR antibody for colorectal cancer,” Lim said.
“The fact that we have been able to successfully combine ERAS15 with panitumumab in three patients, with two of them passing the DLT window, is exciting. And we did that with a 16 milligram dose of ERAS-15, which is within the pharmacologically active dose range of 16 to 32 milligrams. It’s really exciting to have safety and tolerability that is promising with that combination and activity within the PAD.”
The Erasca-Revolution dispute appears to explain a decline early this past week in the American depositary shares of another cancer drug developer whose pipeline includes RAS-targeting therapies: Adlai Nortye (NASDAQ: ANL) shares skidded 10.5% from $14.80 to $13.25 the day of Erasca’s announcement and filing, then dropped another 8% to $12.17 Tuesday before rebounding 27% the rest of the week, closing Friday at $15.50.
Adlai Nortye is developing AN9025, an oral, small-molecule pan-RAS(ON) inhibitor designed to treat a variety of advanced solid tumors with RAS mutations. AN9025 is under study in a Phase I trial (NCT07252479) whose first patient was dosed in the United States in February. The trial is being conducted with Jiangsu Aosaikang Pharmaceutical, which holds rights to AN9025 in China, Hong Kong, and Macao.
Andrew Berens, MD, senior managing director, targeted oncology, and a senior research analyst with Leerink Partners, wrote in a research note that a conversation with Adlai Nortye management offered reasons for confidence that the company will avoid legal trouble in connection with AN9025.
“ANL’s discovery of AN9025 was conducted in-house and independently, suggesting that trade secret misappropriations are unlikely,” Berens reported. “Further, while both drugs feature a macrocyclic scaffold, according to ANL, ERAS-0015 has significantly less branch change modifications and features a bridge, while 9025 underwent numerous branch modifications and the addition of a ring to the scaffold.”
Leaders and laggards
- Esperion Therapeutics (NASDAQ: ESPR) shares leaped 55.5% from $2 to $3.11 Friday after the developer of cardiometabolic and rare/orphan disease therapies said it agreed to be acquired by funds managed by the healthcare-focused investment firm Archimed in a deal valued at up to approximately $1.1 billion if Esperion achieves specified commercial-based milestones. Esperion shareholders will receive $3.16 per share in cash at closing, plus the right to participate in contingent milestone payments of up to $100 million tied to future U.S. net sales for products containing bempedoic acid and products containing bumetanide. The upfront cash consideration represents a premium of 58% to Esperion’s closing share price on Thursday. Founded in 2008, Esperion specializes in developing drugs designed to fight the risk of cardiovascular disease. Esperion’s board has unanimously approved the acquisition deal, which is expected to close in the third quarter of 2026, subject to customary closing conditions that include approval by Esperion’s shareholders and required regulatory approvals.
- Novocure (NASDAQ: NVCR) shares jumped 27% from $11.93 to $15.21 Thursday following several positive announcements by the oncology drug/device developer. Novocure raised its 2026 guidance to investors, increasing its net revenue forecast range to $690 million–$710 million (from $675 million–$705 million), and adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) from a $15 million operating loss to zero (from a $20 million operating loss to zero). The company said its launch of Optune Pax®, a wearable device designed to deliver its Tumor Treating Fields (TTFields) therapy for adults with locally advanced pancreatic cancer concomitant with gemcitabine and nab-paclitaxel, was successful, with 800+ prescribers certified and 160+ prescriptions received through March 31. TTFields are alternating electric fields designed to cause cell death by disrupting cancer cell replication. Novocure finished Q1 with net revenue of $174.055 million, up 12% year-over-year from $154.994 million.
- Sangamo Therapeutics (NASDAQ: SGMO) shares plummeted 35% from 20 cents to 13 cents on Wednesday after the genomic medicine developer said it will begin trading its shares on the OTCQB Venture Market on May 5, under its existing ticker symbol SGMO. The switch comes after Nasdaq notified Sangamo that its common stock will be delisted from the Nasdaq Capital Market due to non-compliance with Nasdaq’s minimum $1 per share bid price requirement. While Sangamo said it intends to request a hearing from Nasdaq to appeal the delisting determination, that hearing will not stay the suspension of trading of Sangamo’s common stock. Sangamo said the shift is not expected to result in material impacts to its business or operations: “Sangamo remains focused on pursuing opportunities to raise additional capital, including an assessment of all strategic options to maximize the value of its assets.” To that end, the company said, it is negotiating “multiple potential business development transactions.”
- uniQure (NASDAQ: QURE) shares climbed 19% from $16.73 to $19.95 Thursday after the gene therapy developer offered regulatory updates that included having been granted a granted a Type B meeting with the FDA to occur in the second quarter: “The company expects to discuss key elements of a potential Phase III trial design and to receive feedback on the proposed statistical analysis plan for the four-year analysis expected in the third quarter.” uniQure added that it held a pre-submission meeting with the U.K.’s Medicines and Healthcare Products Regulatory Agency (MHRA) and plans to submit a Marketing Authorization Application (MAA) for AMT-130 for the treatment of Huntington’s disease in the third quarter. The company said it expects to submit an MAA based on a three-year analysis from its ongoing U.S. and European Phase I/II clinical trials.
The post StockWatch: Patient Death, Rival’s Patent Challenge Sink Erasca Shares appeared first on GEN – Genetic Engineering and Biotechnology News.
Data-Driven Tool Identifies Individuals at Highest Risk of Obesity-Related Disease
A new clinical risk model may transform how obesity is managed, by identifying which individuals are most likely to develop serious complications, regardless of their body mass index (BMI).
Developed by researchers at Queen Mary University of London and the Berlin Institute of Health, the tool, called OBSCORE, uses just 20 routinely collected clinical variables to predict the future risk of 18 obesity-related conditions, ranging from type 2 diabetes to cardiovascular disease.
Published in Nature Medicine, the study challenges the long-standing reliance on BMI as the primary metric for assessing obesity-related health risk.
Moving beyond BMI
BMI has long served as a simple proxy for obesity, but it fails to capture the biological heterogeneity of patients. Two individuals with similar BMI can have vastly different risks of developing complications.
The new model addresses this limitation directly. As described in the study, it “provides information beyond BMI” by integrating multiple dimensions of health into a unified risk score.
These include demographic data, clinical biomarkers, disease history, and lifestyle factors, variables already commonly available in healthcare settings.
The findings show that BMI alone is a poor discriminator of risk. The model consistently outperformed BMI-based approaches across all tested outcomes.
Large-scale data enables precision risk prediction
To build the model, researchers analyzed health data from nearly 200,000 individuals with overweight or obesity from the UK Biobank.
Using an interpretable machine learning framework, they screened more than 2,000 potential predictors and distilled them into a core set of 20 features that best predicted long-term health outcomes.
The resulting OBSCORE model estimates the 10-year risk of developing 18 conditions, including cardiovascular disease, kidney disease, sleep apnea, and metabolic disorders.
The model demonstrated strong predictive performance, with median concordance indices around 0.75 across outcomes, indicating robust discrimination between high- and low-risk individuals.
Hidden high-risk individuals
One of the most striking findings is that high-risk individuals are not always those with the highest BMI.
A substantial proportion of individuals classified as high risk fell into the “overweight” category (BMI 27–30 kg/m²), rather than obesity. In some outcomes, up to ~40% of those in the highest risk group had BMI below the obesity threshold.
This reveals a critical gap in current clinical practice: individuals who may benefit from intervention could be overlooked simply because they do not meet BMI-based criteria.
On the other hand, some individuals with obesity may have relatively low risk and may not require intensive intervention.
Strong risk stratification across diseases
Beyond prediction, the scientists believe that OBSCORE enables meaningful risk stratification. Individuals in the highest risk group showed dramatically higher rates of disease compared to those in the lowest group.
For example, the study reports:
- Up to 89-fold higher risk for chronic kidney disease
- 42-fold higher risk for type 2 diabetes
- 47-fold higher risk for cardiovascular mortality
These differences exceed those observed when comparing individuals based solely on BMI categories, underscoring the added value of multidimensional risk assessment.
Clinical and healthcare implications
The implications of these findings are significant, particularly in the context of emerging obesity therapies.
Highly effective drugs such as GLP-1 receptor agonists and dual incretin therapies have transformed treatment options, but their high cost and limited availability make patient prioritization essential.
As the authors note, current systems lack robust frameworks to identify which patients should receive treatment.
OBSCORE offers a potential solution by enabling risk-based allocation of interventions, ensuring that treatment is directed toward those most likely to benefit.
This could improve clinical outcomes while optimizing healthcare resource use.
Toward implementation in clinical practice
One of the key strengths of OBSCORE is its practicality. Unlike many predictive models, it relies on a small number of variables that are already routinely collected, making it suitable for integration into electronic health records.
The researchers envision the model being used as a decision-support tool in clinical settings, complementing rather than replacing existing frameworks.
External validation in independent cohorts—including populations of different ancestry, demonstrated strong generalizability, further supporting its potential for real-world deployment.
Limitations and next steps
Despite its promise, the model requires further validation in broader populations, including younger individuals and more diverse healthcare settings.
Additionally, while OBSCORE effectively stratifies risk, translating these predictions into actionable treatment thresholds will require clinical consensus and cost-effectiveness analyses.
The authors also emphasize that the model identifies predictive, not necessarily causal, factors, and should be interpreted accordingly.
Taken together, the findings mark a shift toward precision medicine in obesity, moving from simplistic metrics like BMI to data-driven, individualized risk assessment.
By capturing the complex interplay of metabolic, clinical, and behavioral factors, OBSCORE could enable earlier intervention, better targeting of therapies, and improved long-term outcomes for patients living with overweight and obesity.
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Meta-analysis of the effects of exercise intervention on physical health in individuals undergoing compulsory isolation
BackgroundPhysical health is the basic indicator to evaluate the health of drug addicts after the process of drug rehabilitation. In order to better improve the deficiency degree of physical health of drug addicts, it is necessary to carry out a systematic review.ObjectiveTo explore the effects of exercise intervention on the physical health of individuals undergoing compulsory drug rehabilitation using Meta-Analysis, aiming to provide evidence-based support for improving their physical health.MethodsRandomized controlled trials (RCTs) published between 2019 and December 2024, examining the impact of exercise intervention on the physical health of compulsory detoxification individuals, were retrieved from databases including Web of Science, PubMed, Cochrane Library, Medline, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Chinese Journal Database. The quality of included studies was assessed using the Cochrane risk-of-bias assessment tool. RevMan 5.4 software was employed for heterogeneity testing, effect size synthesis (using mean difference [MD] and 95% confidence interval [CI]), and generation of forest plots, funnel plots, and quality assessment diagrams. Subgroup analyses were performed to evaluate sensitivity and heterogeneity of the included studies.ResultsExercise intervention effectively improved the physical health of compulsory drug rehabilitation individuals, particularly in physical fitness indicators: sit-and-reach test [MD = 3.92, 95%CI = (3.23, 4.62), P<0.001], single-leg standing with eyes closed [MD = 7.03, 95%CI = (6.05, 8.02), P<0.001], grip strength [MD = 1.23, 95%CI=(0.06, 2.39), P = 0.04], and choice reaction time [MD=-0.03, 95%CI=(-0.05, -0.01), P = 0.002]. Improvements in physical function were also observed; however, the increase in vital capacity [MD = 86.81, 95%CI=(-1.56, 175.17), P = 0.05] did not reach statistical significance.ConclusionThis meta-analysis provides evidence that exercise intervention significantly improves specific physical health deficits—namely flexibility (sit-and-reach), balance (single-leg stance), muscular strength (grip strength), cardiopulmonary function (vital capacity), and sensorimotor coordination (choice reaction time)—in individuals undergoing compulsory rehabilitation. It is recommended to adopt a combination of aerobic and traditional fitness exercises, with at least 3 sessions per week, each lasting no less than 40 minutes, and a duration of over 12 weeks, providing scientific evidence for drug rehabilitation practices. These indicators were selected because they directly reflect the multisystem damage (muscular, neural, and cardiorespiratory) caused by chronic substance use. However, this study acknowledges the limitation that psychological and neurocognitive outcomes (e.g., cravings, mood, executive function), which are crucial in addiction treatment, were not included in the eligibility criteria and systematic analysis. The follow-up research will combine physical and psychological indicators to conduct a comprehensive evaluation of the intervention effect of exercise on drug rehabilitation.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420251029820.