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.
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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.
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”
Jonathan E. Lim, MD, Erasca’s chairman, CEO, and co-founder
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 back17% 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.
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.
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.
Cell and gene therapy encompasses a broad range of therapeutic interventions for diseases that have proved refractory to treatment with conventional pharmaceutical approaches. Perhaps the most familiar FDA-approved modality in the cell and gene therapy field is chimeric antigen receptor (CAR) T-cell therapy, which involves genetic modification of a patient’s own T cells to identify and eliminate malignant cell lineages in acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma.
Although only 20 or so cell or gene therapies have been FDA-approved, the area holds considerable promise for investment. The global market was valued at nearly $9 billion in 2025, and growth has been projected at over 15% per year from 2026 to 2035. As with any pharmaceutical product, however, the potential of cell and gene therapy relies in large part upon minimizing risks to patient health from adverse effects. Numerous companies, from both prominent names in the field to smaller startups, are developing solutions to mitigate the deleterious consequences of cell and gene therapy.
Reducing cytokine release syndrome
Cytokines are a broad family of small proteins and peptides that cell lineages of the innate and adaptive immune systems employ to communicate with each other and coordinate timely and appropriately scaled responses to foreign antigen-containing cells. Cytokine release syndrome (CRS) occurs when hyperactivation of one or more immune lineages results in the release of excessive quantities of cytokines into the circulation.
“As a scientific community, we’ve been researching CAR T-cell therapy for over 30 years and have grown together in our understanding of the body’s immune response to treatment, from both a safety and efficacy perspective,” says Rosanna Ricafort, MD, vice president and global program lead of hematology and cell therapy at Bristol Myers Squibb. “We have evolved our ability to characterize, stage, and manage potential side effects, allowing for timely and thoughtful interventions of the most commonly associated side effects like CRS.”
Ricafort cited clinical data presented at the 2025 American Society for Clinical Oncology (ASCO) meeting in Chicago demonstrating that over 95% of instances of CRS and other adverse events arising from BMS’s CD19-directed CAR T-cell therapy (BreyanziR) occurred in the first two weeks after onset of therapy. “These and other studies have helped establish the largely predictable safety profile of CAR T-cell therapy to date,” Ricafort pointed out.
Minimizing side effects
The NF-κB and prostaglandin E2 pathways are prominent regulators of the activation and differentiation of pro-inflammatory T cell lineages. Excessive signaling through these pathways results in cytokine amplification, which contributes to CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), a complication of some types of CAR T-cell therapy.
CytoAgents, a clinical-stage biotech company, is developing CTO1681, an orally administered prostaglandin signaling inhibitor that has been shown to offset CRS and ICANS toxicities associated with CAR T-cell therapy of lymphoma patients. At the 2025 European Society for Medical Oncology (ESMO) Immuno-Oncology Congress in London, CytoAgents presented non-clinical data showing that CTO1681 treatment reduced secretion of TNF-α, IL6, and other key CRS-associated cytokines with no impairment of CAR T-cell mediated cytotoxicity on lymphoma cells.
“These data suggest CTO1681 could enable safer CAR T-cell therapy administration, support outpatient treatment paradigms, and broaden patient access without compromising anti-tumor efficacy,” said Teresa Whalen, CEO at CytoAgents. CTO1681 is currently in Phase Ib/IIa trials for cancer patients undergoing CAR T-cell therapy, with potential expansion into additional therapeutic spaces including asthma and chronic obstructive pulmonary disease.
Adding immunosuppressants
A potential side effect of adeno-associated virus (AAV)-based gene transfer approaches is acute liver injury resulting in part from CRS in patients receiving AAV therapy. Duchenne muscular dystrophy (DMD) is a progressive, degenerative muscular disorder caused by mutations or changes in the DMD gene, resulting in reduced levels of the protein dystrophin.
Credit: Kateryna Con / Getty Images / Science Photo Library
Elevidys, developed by Sarepta Therapeutics, is an AAV-based therapy approved for the treatment of DMD that stimulates targeted production of a truncated form of dystrophin in skeletal muscle. “Individuals with non-ambulatory Duchenne face profound unmet need and fewer treatment options,” says Louise Rodino-Klapac, PhD, president of R&D and development and technical operations at Sarepta. Topline data released earlier this year showed that Elevidys treatment resulted in significant improvement in key clinical ambulatory metrics in patients.
As part of its ENDEAVOR clinical trial, Sarepta Therapeutics is evaluating the potential of supplementing Elevidys with sirolimus to reduce potential acute liver injury (ALI) complications. Sirolimus is a mammalian target of rapamycin (mTOR) kinase inhibitor that suppresses responses of T and B cells to interleukin 2, which functions to stimulate proliferation of helper, cytotoxic, and regulatory T cells.
Developing non-integrating therapies
As an alternative approach to supplementing cell and gene therapy modalities with existing immunosuppressants, other companies are modifying CAR T-cell therapy to reduce the risk of CRS and other side effects. Myasthenia gravis, a chronic fatigue-inducing autoimmune disorder in which signals between nerves and muscles are compromised, results in part from the secretion of autoantibodies from B-cell maturation antigen (BCMA)-expressing B plasma cells.
Conventional BCMA-directed CAR T-cell approaches rely on the integration of lentiviral or gamma-retroviral vectors to encode the CAR and typically involve lymphodepletion chemotherapy that can be accompanied by acute and delayed toxicity. In contrast, non-integrating (i.e., mRNA-based) BCMA-directed CAR T-cell therapies may circumvent this toxicity due to the lack of requirement for chemotherapy.
Cartesian Therapeutics is developing an mRNA-based BCMA-targeted CAR T-cell therapy for myasthenia gravis, Descartes-08. At the 2025 American Academy of Neurology (AAN) Annual Meeting in San Diego, results were reported of a Phase IIb clinical trial of Descartes-08 in myasthenia gravis. In the trial, adverse event rates were similar between groups receiving Descartes-08 and the placebo group, and were predominantly mild to moderate in nature, with no cases of CRS or ICANS reported.
“The impressive strength and duration of response shown in the data reinforce our confidence in the potential of Descartes-08 to transform the current treatment landscape in MG, offering patients a safe, flexible, and durable treatment option,” said Carsten Brunn, PhD, president and CEO of Cartesian.
Engineering chimeric receptors
Modifications of CAR T-cell therapy to improve clinical efficacy and reduce side effects can also encompass modification of the molecular structure of the chimeric receptor itself. D domains are highly selective targeting domains incorporated into newer generations of CARs that enhance targeting of pathological cell types and reduce immunogenic responses in patients that give rise to unwanted side effects.
One example of such next-generation CAR T-cell therapies, anito-cell, has been co-developed by Arcellx, Kite Pharma, and Gilead. Anito-cel is an autologous anti-BCMA CAR T-cell therapy for the treatment of relapsed/refractory multiple myeloma patients.
Phase II trial results in multiple myeloma presented at the 2025 American Society of Hematology (ASH) meeting in Orlando showed an overall response rate of 97% and a complete response rate of 68%. Importantly, in the context of side effects, there were no delayed neurological symptoms, and for most patients, only low-grade CRS was observed, which was resolved within a few days.
“The anito-cel D-domain BCMA binder could be important to our work in in vivo cell therapy, further strengthening our potential in oncology and inflammation,” said Daniel O’Day, chairman and CEO of Gilead. “Anito-cel could become a foundational treatment for multiple myeloma over time, including earlier lines of therapy.”
Chair, Advanced Therapeutics University of Edinburgh, U.K.
Carrie Haverty
Vice President of Medical Affairs & Clinical Strategy Mirvie
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Welcome to the 2026 State of Precision Medicine virtual summit, hosted by Inside Precision Medicine. This year’s summit focuses on the existing gaps in precision medicine as we ask: How do we make treatment equitable and accessible for all patients across the disease continuum?
On June 3rd, the editors of Inside Precision Medicine will feature an outstanding line-up of guests highlighting the challenges and urgency of expanding access to disease therapies and empowering patients and consumers.
Agenda Highlights:
Becky Quick, co-anchor of CNBC’s Squawk Box and the founder of CNBC Cures, discusses her own family’s rare disease journey and her prescription to expand access to rare disease therapeutics
Anne Wojcicki, CEO of the 23andMe Research Institute, speaks on the consumer genetics pioneer’s recent renaissance leading the newly re-imagined organization
Brian Bigger, PhD, and Rob Wynn, MD, scientists and clinicians at Manchester University, share insights from their work on stem cell gene therapy and its potential to offer hope for patients with rare diseases such as Hunter syndrome. They are joined by Ricky Chu, father of two children with Hunter syndrome, a rare neurodevelopmental disorder
Carrie Haverty, president of the National Society of Genetic Counselors, hosts a panel on the current trends and challenges in genetic counseling
Saralyn Mark, MD, first senior medical advisor to both the Office on Women’s Health within the HHS and NASA, boldly explores lessons in women’s health with her guests Dorit Donoviel, PhD, and Kim Templeton, MD
Breakout sessions from the summit sponsors, including 10x Genomics and Illumina
Registration is entirely free. We look forward to seeing you on June 3.
Officials at Ecolab Life Sciences report that the company is expanding its bioprocessing business with the launch of a new bioprocessing applications lab (BPAL) in Dongtan, Korea. They say the goal is to provide biopharmaceutical manufacturers across Asia with better local access to downstream process development support.
The site is Ecolab’s first bioprocessing facility in Asia and joins an established applications network in the U.S. and U.K.
BPAL Korea supports process development from early-stage resin screening through studies designed to replicate commercial manufacturing conditions, according to Jenny Tan, vice president and general manager, Ecolab Life Sciences APAC and India. On-site scientists work alongside customers across Asia to help optimize chromatography steps, improve yield and productivity, and accelerate regulatory pathways, with the aim of reducing the need to ship resins and reference materials overseas for development work, she continues.
Asia has become one of the world’s most active biopharmaceutical manufacturing regions, with Korea, China, Japan, India, and Singapore all home to growing pipelines in biosimilars and monoclonal antibody processes that scalable downstream purification. With local technical support now in place, manufacturers across the region can shorten development cycles and maintain consistency with global operations while working to tight regulatory and cost targets, continues Tan.
“Biopharmaceutical manufacturers across Asia are under increasing pressure to scale with speed while meeting demanding regulatory and performance expectations,” she explains. “BPAL Korea strengthens our ability to work side by side with customers, bringing local expertise together with Ecolab’s global, integrated bioprocessing network.”
By combining local scientific support with Ecolab’s innovative Purolite resin portfolio, Ecolab’s new BPAL was created to help enable manufacturers to address process challenges earlier, reduce development risk, and advance programs with greater confidence as they prepare for scaleup, says Tan.
Body mass index has its limitations, but for now it’s the metric medicine often defaults to when predicting weight-related health problems. A new tool promises to better define who’s at risk for obesity complications, based on measures that include BMI but also family history, diet, current illness, and socioeconomic factors culled from medical records.
One aim of the research is to better understand who’s a candidate for an obesity drug, often prescribed based on BMI alone or BMI in combination with another disease. Over time, GLP-1 medications, whose initial target was type 2 diabetes, have revealed their power to ease cardiovascular disease, kidney disease, liver disease, sleep apnea, and osteoarthritis, in addition to promoting significant weight loss. But discerning who’s the best fit for the costly, lifelong treatment has been uncertain.
“We really wanted to have an integrated model that enables us to look at not one, but 18 different obesity-relevant complications,” Claudia Langenberg, co-author of a study about the new model published Thursday in Nature Medicine, said in a media briefing Tuesday. She is director and professor of medicine and population health at Precision Healthcare University Research Institute of Queen Mary University of London.
Cases of bowel and ovarian cancer are rising, but only among people under 50, according to research published in the British Medical Journal Oncology today, April 28, 2026. While other types of cancer are also rising in older adults, this particular trend among younger adults is striking.
A key factor, the researchers’ work suggests, is excess weight. But that does not fully explain the trends they saw.
In particular, there was a significant rise in 11 cancers among the younger adults with known behavioral risk factors. These cancers were: thyroid, multiple myeloma, liver, kidney, gallbladder, bowel, pancreatic, womb lining (endometrial), mouth, breast, and ovarian cancers.
Rates of all these cancers also rose significantly among the older adults, with the notable exceptions of bowel and ovarian cancers.
Besides mouth cancer, all 11 cancers associated with known behavioral risks were linked to obesity. And six (liver, bowel, mouth, pancreas, kidney, and ovary) were also linked to smoking; four (liver, bowel, mouth, and breast) were associated with alcohol intake; three (bowel, breast, and endometrial) were linked to physical inactivity; and one (bowel) was associated with dietary factors.
“Of the 11 cancers we identified which were increasing and linked to known lifestyle factors—the most common by far in younger adults was breast cancer,” the study’s lead author, professor Montserrat Garcia-Closas, MD, DrPH, told Inside Precision Medicine. Garcia-Closas is in Integrative Cancer Epidemiology, Division of Genetics and Epidemiology, and The Cancer Epidemiology and Prevention Research Unit, The Institute of Cancer Research, London.
The rising incidence of certain cancers among people under 50 isn’t unique to England, and one major question is whether changes in behavioral risk factors might be to blame.
This research group analyzed cancer incidence trends in England from the National Disease Registry Service for the period 2001 to 2019, comparing patterns by sex in two age groups: 20–49 year olds and those aged 50+ for more than 20 different cancer types.
This database, “Captures virtually every cancer diagnosis in England going back decades—one of the most complete registries in the world. That scale is what allows us to track trends reliably across the whole population, not just a sample,” said Garcia-Closas.
The team used national health surveys to look at trends in established risk factors: smoking, alcohol intake; diet (high red/processed meat, low fiber intake), excess weight (BMI), and physical inactivity to quantify any changes by age and sex and estimate the proportion of cancers attributable to specific risk factors.
Their analysis showed that new cases of 16 out of 22 cancers in younger women, and 11 out of 21 cancers in younger men, increased significantly in England between 2001 and 2019.
And five cancers—endometrial, kidney, pancreatic, multiple myeloma, and thyroid cancer— increased significantly faster in younger than in older women, while multiple myeloma increased faster in younger than in older men.
But with the exception of excess weight, trends in these risk factors over the past one to two decades have been stable or improving for younger adults, with the largest reductions of around 7% in red meat consumption.
The average daily amount of red meat eaten, they report, fell from 38 grams in 2008 to 17 grams in 2018 among younger men, and from 22 grams to 10 grams in younger women. And average processed meat intake in younger women was half that of younger men: 10 grams versus around 20 grams. And while more than 90% of younger adults weren’t eating enough fiber in 2018, their intake remained stable or slightly improved in both sexes between 2009 and 2019. And these trends were similar in older adults.
Established behavioral risk factors accounted for a substantial share of cancer cases. In 2019 these contributed 68%–65% of mouth cancers for younger and older men, respectively; 42%–48% of liver cancers; 49%–53% of bowel cancers, 29%–33% of kidney cancers, and 36%–34% of pancreatic cancers.
Among women they accounted for 52%–45% of mouth cancers; 35%–42% of endometrial cancers; 44%–46% of liver cancers; 38%–42% of bowel cancers; 33%–37% of kidney cancers; 31%–28% of pancreatic cancers; and 19% to 24% of gallbladder cancers.
Excess weight was the risk factor associated with most cancers in 2019, ranging from 5% for ovarian cancer to 37% for endometrial cancers.
“These patterns suggest that while similar risk factors across ages are likely, some cancers may have age-specific exposures, susceptibilities, or differences in screening and detection practices,” write the researchers.
“Prevention takes a long time and we must act now with what we know, with better and more effective public health policy and programs to address the overweight and obesity epidemic,” said Garcia-Closas.
BackgroundNeurite orientation dispersion and density imaging (NODDI), an emerging diffusion MRI technique for estimating the microstructural pathology of brain tissue in vivo, has attracted significant research interest. However, a systematic bibliometric analysis of this field remains unexamined. This study aims to perform a bibliometric analysis of the NODDI literature to explore the current research landscape, identify emerging trends, and provide insights for future investigations.MethodsNODDI-related publications were retrieved from the Web of Science (WOS) and Scopus databases during the period of 2012 to 2025. CiteSpace, VOSviewer, and Bibliometrix R package were used to generate visualization maps.ResultsA total of 679 publications related to NODDI were identified from WOS, including 653 research articles and 26 review papers. 844 relevant publications were retrieved from the Scopus database. After 2012, the number of publications on NODDI increased rapidly. Sweden demonstrated the highest average citation per paper, while the United States contributed the largest number of publications. University College London was the most productive institution. Hui Zhang was identified as the most prolific author, while Alexander DC achieved the highest average citation count. NeuroImage was recognized as the leading journal in terms of publication frequency. Common keywords included “diffusion magnetic resonance imaging,” “NODDI,” “brain,” and “multiple sclerosis.” Recent studies show the research focus is shifting from methodological development to clinical application, especially in the field of neuropsychiatric disorders, and is being integrated with emerging methodologies such as Mendelian randomization.ConclusionsThis bibliometric analysis highlights potential directions for future NODDI-related research. Future studies may focus on optimizing imaging techniques, investigating neuropsychiatric disorders, and integrating advanced methodologies.
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.
