Author: admin

Posted on

DNA Tests to Predict GLP-1 Drug Response to Launch in 2026

PrecisionLife and Ovation.io have signed a commercialization agreement to bring GLP-1 response genetic tests to the market. Today, the partners announced plans to launch both direct-to-consumer and laboratory developed tests later this year. 

The companies had entered a collaboration at the end of last year, leveraging Ovation’s multi-omics and longitudinal clinical data and PrecisionLife’s advanced analytics platform to uncover genetic mechanisms of response to GLP-1 medication. Earlier this year, they reported the identification of a series of biomarker signatures that can quantitatively predict which patients are most likely to respond to GLP-1 therapies and sustain that response over time. 

The partners are now actively working on translating this discovery into noninvasive genetic tests for patients to make informed decisions about the likely risks and benefits of these increasingly popular drugs, as well as for drug developers to stratify patients in clinical trials.

“Our teams have generated the world’s most detailed insights into why patients respond differently to these medicines,” said Steve Gardner, chief executive officer of PrecisionLife. “We will make these insights clinically actionable via noninvasive DNA tests supported by our results reporting platform and CLIA lab partners.”

PrecisionLife stressed that their findings go beyond the GLP-1 genetic predictors reported last week by 23andMe. “While that study highlighted a handful of variants associated with modest differences in outcomes, this work identifies combinatorial biomarker signatures that stratify patients and quantitatively predict response—and is already being translated into tests designed for use in real treatment decisions,” a company representative told Inside Precision Medicine. 

Over the course of the next six months, PrecisionLife will reproduce, refine, and validate their findings using additional datasets provided by Ovation, including studies to confirm the predicted response to GLP-1 drugs including semaglutide and tirzepatide in a real-world context. 

The launch of a consumer DNA test is expected to enable patients to understand their individual safety, efficacy, and tolerability profile for GLP-1 drugs before starting treatment. This could also offer providers a clearer basis for selecting therapies and help payors make more sustainable coverage decisions. The collaborators have stated they will evaluate the opportunity of using these tests to inform reimbursement decisions and expand coverage of certain health plans based on an individual’s predicted response. 

For drug developers, laboratory developed tests (LDT) could open up opportunities for more precise patient stratification, improving the probability of success in clinical trials evaluating the expansion of GLP-1 drugs into new indications. The companies are currently in discussions with various stakeholders and sponsors to deploy the LDTs as stratification tools in a clinical setting. 

“We’re confident that together we can translate those insights into commercial outcomes and products in GLP-1s and other diseases with huge clinical impact,” said Curt Medeiros, chief executive officer of Ovation.io. 

Going forward, the partners will continue to validate their findings and expand the scope of the studies, including identifying additional markers of safety and tolerability to GLP-1 drugs as well as pinpointing further efficacy and safety signals for individual molecules. 

The post DNA Tests to Predict GLP-1 Drug Response to Launch in 2026 appeared first on Inside Precision Medicine.

Posted on

STAT+: CMS proposes rolling back breakthrough device payment flexibilities

The Centers for Medicare and Medicaid Services is proposing to repeal a pathway that currently allows breakthrough devices to qualify for supplementary payments without proving they provide a substantial clinical improvement over alternatives.

Access to lifesaving new technologies can be stymied when hospitals don’t get paid enough to cover their costs. So since 2001, Medicare has given innovative devices a chance at extra payments when they meet three criteria: they’re new and different from what’s currently available, they offer a clinical improvement over existing options, and they’re especially costly.

Since 2021, devices that receive breakthrough designation from the Food and Drug and Administration have gotten an even sweeter deal: In order to qualify for the extra payments, they only have to demonstrate they’re expensive. 

Continue to STAT+ to read the full story…

Posted on

Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer

A randomized Phase II trial offers a rare signal of progress in pancreatic cancer, a disease long marked by therapeutic stagnation, with investigators reporting that the experimental agent elraglusib (9-ING-41) improved survival when added to standard chemotherapy of gemcitabine plus nab-paclitaxel (GnP).

Published in Nature Medicine, the study evaluated the novel drug—developed within an academic setting at Northwestern University—in patients with metastatic pancreatic cancer. The findings suggest that targeting glycogen synthase kinase-3 beta (GSK-3β), a protein not previously exploited clinically in this disease, could open a new therapeutic avenue.

“This is one of the first trials in a randomized setting that has been positive in pancreatic cancer in the last decade,” said Devalingam Mahalingam, MD, PhD, a study leader at Northwestern University. “There was really a barren spell… many failed trials. So it’s nice to see a positive trial.”

A modest but meaningful survival gain

The multicenter trial enrolled 233 patients across North America and Europe, randomly assigning them to receive chemotherapy alone or in combination with elraglusib. Patients receiving the combination lived a median of 10.1 months compared with 7.2 months for chemotherapy alone, and the addition of elraglusib reduced the risk of death by 38%.

Perhaps more striking, survival at one year doubled in the experimental arm (44% vs. 22%), and approximately 13% of patients remained alive at two years—an uncommon outcome in metastatic pancreatic cancer.

Mahalingam emphasized that the benefit was not necessarily reflected in higher tumor response rates. Instead, patients appeared to derive prolonged disease control.

“We didn’t really see much more tumor shrinkage compared to chemo alone,” he said. “But patients stayed on the treatment arm longer… sometimes they would reduce or drop the chemo and just stay on the drug.”

This pattern, he added, points toward a mechanism beyond direct cytotoxicity.

A different mechanism of action

Unlike conventional chemotherapy, which primarily targets rapidly dividing cells, elraglusib appears to act on the tumor microenvironment—the complex ecosystem of immune cells, stromal tissue, and signaling molecules surrounding cancer cells.

The drug inhibits GSK-3β, a protein involved in multiple cellular processes, including metabolism, signaling pathways, and immune regulation. While broadly expressed in normal tissues, GSK-3β can be co-opted by tumors to promote growth and suppress immune responses.

“GSK-3 beta is expressed in many tumors,” Mahalingam said. “It’s part of a central regulator of normal cell functioning… but in cancer, this pathway is used to allow for tumor growth and proliferation.”

Preliminary analyses from the trial suggest that elraglusib may enhance antitumor immunity. Biopsies and blood-based markers indicated changes consistent with immune activation, supporting the hypothesis that the drug helps re-engage the immune system in a tumor type typically resistant to immunotherapy.

“We saw what we call immunomodulatory effects,” Mahalingam noted. “The immune cells might be driving some of the survival benefit we see.”

This is particularly notable given the long-standing failure of checkpoint inhibitors in pancreatic cancer, a tumor characterized by a highly immunosuppressive microenvironment.

Developed in academia

Elraglusib’s development trajectory also sets it apart. The compound originated in academic laboratories more than a decade ago, with early work spanning Northwestern University, the University of Illinois Chicago, and the Mayo Clinic.

“This is what not many drugs are—developed within an academic setting,” Mahalingam said. “It was founded in a chemistry lab… and then moved into a spin-off company to raise funding for trials.”

After preclinical development between 2010 and 2015, the drug entered early-phase trials around 2017 and has since been evaluated across multiple tumor types, with a recent focus on pancreatic cancer.

The randomized Phase II trial marks the first time a GSK-3β inhibitor has demonstrated efficacy beyond early-stage testing.

Broad eligibility, real-world relevance

Investigators designed the study with relatively broad inclusion criteria, enrolling patients with high tumor burden and poor nutritional status—characteristics common in real-world pancreatic cancer populations but often excluded from clinical trials.

“We allowed patients with very large volumes of disease,” Mahalingam said. “We did not restrict patients for albumin… we didn’t engineer the study to look better.”

This approach may partly explain the modest median survival difference, as some patients progressed too quickly to benefit. However, it also strengthens the generalizability of the findings.

Safety and next steps

Side effects associated with elraglusib were generally manageable and consistent with chemotherapy, including hematologic toxicities, fatigue, and reversible vision changes.

The next step will be a confirmatory Phase III trial, with discussions ongoing with regulators.

“We really need to confirm the studies in a large phase three trial,” Mahalingam said, adding that trial design considerations include how to integrate emerging therapies such as KRAS inhibitors.

Investigators are also exploring combination strategies, including pairing elraglusib with immunotherapy or alternative chemotherapy regimens. Early safety studies suggest such combinations are feasible, though efficacy data remain limited.

Potential beyond pancreatic cancer

Given the central role of GSK-3β in multiple cellular pathways, researchers are already investigating the drug’s potential in other malignancies, including hematologic cancers and pediatric tumors such as Ewing sarcoma and medulloblastoma.

“This is a new class of potential cancer therapeutics,” Mahalingam said. “Certainly, there would be excitement in seeing where this target can be applied to other tumors.”

While challenges remain, the trial’s results offer cautious optimism in a field where progress has been incremental at best.

“Even if it means that this class of drugs can be used for future drug development,” Mahalingam said, “it gives an opportunity to expand therapeutic potential—not just for pancreatic cancer, but beyond.”

The post Elraglusib Delivers Rare Survival Benefit in Pancreatic Cancer appeared first on Inside Precision Medicine.

Posted on

Public Perceptions of AI in Medicine and Implications for Future Medical Education: Cross-Sectional Survey

Background: The integration of artificial intelligence (AI) into clinical practice is contingent on public trust. This trust often depends on physician oversight, yet a significant gap exists between the need for AI-competent physicians and the current state of medical education. While the perspectives of students and experts on this gap are known, the views of the US general public remain largely unquantified. Objective: This study aimed to assess US public perceptions regarding AI in medicine and the corresponding emergent needs for medical education. We specifically sought to quantify public trust in different diagnostic scenarios, concerns about physician overreliance on AI, support for mandatory AI education, and priorities for the future focus of medical training. Methods: We conducted a cross-sectional, web-based survey of adults in the United States in November 2025. Participants (N=524) were recruited via SurveyMonkey Audience. We calculated descriptive statistics, frequencies, proportions (percentages), and 95% CIs for all main survey items. Results: A total of 524 participants completed the survey. Most (n=329, 62.8%; 95% CI 58.6%‐66.9%) placed the most trust in a physician’s diagnosis based on their expertise alone; only 7.8% (n=41; 95% CI 5.5%‐10.1%) trusted an AI-first diagnostic model. Trust was highly contingent on training: 93.9% (n=492) of participants rated formal physician training on AI limitations as “essential” or “very important.” Widespread concern about physician overreliance on AI was reported, with 81.1% (n=425) being “very concerned” or “extremely concerned.” Consequently, 85.1% (n=446) agreed or strongly agreed that training on AI use, ethics, and limitations should be mandatory in medical school. When asked about future educational priorities, 70.2% (n=368; 95% CI 66.3%‐74.1%) believed that medical education should focus on human-centered skills (eg, empathy and communication) over clinical skills. Conclusions: The US public expressed conditional trust in medical AI, strongly preferring physician-led and critically supervised models. These findings reveal a clear public mandate for medical education reform. The public expects future physicians to be mandatorily trained to appraise AI, understand its limitations, and refocus their professional development on the human-centered skills that technology cannot replace.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/3874abd2d5f25c78f21987a16f3af6be" />

Posted on

Motoneurons Inhibitory Synapses Homeostatically Respond to Neuronal Activity and Modulate Amyotrophic Lateral Sclerosis Pathogenesis

Alterations in excitation/inhibition (E/I) balance and changes in motor neurons (MN) activity may contribute to MN vulnerability in ALS. The balance of pathogenic versus adaptive changes occurring in inhibitory synapses and affecting E/I balance remain unclear. Confocal microscopy of MN from P45 male SOD1G93A mice reveal downregulated GlyR but upregulated GABAR clusters at inhibitory synapses. GlyR and GABAR respond to PSAM and DREADD chemogenetic alterations of MN excitability, with increased activity driving increase in inhibitory clusters. An E3 ligase-conjugated intrabody (GFE3) degrades Gephyrin, decreases GABAR and GlyR clusters, increases net activity, and downregulates disease markers. However, simultaneous decrease of inhibition and increased activity by actPSAM and GFE3 shows no net beneficial effects on disease markers. Thus inhibitory synapses are involved in the early phases of ALS pathogenesis and respond to persistent homeostatic loops, and their suppression delivers a net activity increase, offering potential benefits on disease pathways.

Posted on

ThermoCas9: Gene Editor Targets Cells with Disease-Related Hypomethylation

Research led by Wageningen University in the Netherlands and the Van Andel Institute (VAI) in Michigan has shown that ThermoCas9, a variant of CRISPR, can distinguish tumor DNA from healthy DNA and selectively cut only the former, marking a potential step toward a highly precise cancer therapy.

The method relies on DNA methylation, a process in which methyl groups are added to DNA to regulate whether genes are on or off. In cancer cells, DNA methylation is altered and can therefore act as a molecular “fingerprint” that differentiates tumor cells from healthy ones.

“ThermoCas9 is the first CRISPR-associated enzyme to respond to differences in the most abundant type of DNA methylation in human and other eukaryotic cells,” explained co-senior author John van der Oost, PhD, from Wageningen University. “This means we now have a system that we can target specifically toward tumor cells.”

The study, published in Nature, represents the first time a CRISPR-based method has relied on methylation to target human cancer cells.

“ThermoCas9 uses methylation like an address to precisely target cancer cells while leaving healthy cells untouched,” added co-senior author Hong Li, PhD, from VAI. “The findings could be a game changer.”

After analyzing ThermoCas9’s structure and finding that it can distinguish between unmethylated and methylated genes, Li and team introduced the enzyme into different types of healthy human cells with distinct methylation landscapes and into breast and colorectal cancer cells.

They found that ThermoCas9 cut DNA in the tumor cells while leaving healthy DNA intact, suggesting that the system can detect subtle chemical differences between healthy and tumor cells and act on them.

“ThermoCas9 is a perfect example of the value of fundamental research; you have to know how these individual pieces work together,” said Li. “We used biochemistry and structural biology to discover a mechanism that we one day hope will lead to more precise, effective cancer treatment.”

Although the study highlights the potential of ThermoCas9 as a cancer treatment, it does not show that the selective DNA damage it inflicts leads to tumor cell death. The researchers next steps will focus on damaging tumor DNA sufficiently to trigger cell death.

Of note, aberrant methylation patterns also play a role in diseases other than cancer, including autoimmune disorders. It is therefore possible that ThermoCas9 or a similar CRISPR tool could evolve into a versatile molecular strategy that recognizes diseased cells by their chemical “signature” and selectively disables them.

The post ThermoCas9: Gene Editor Targets Cells with Disease-Related Hypomethylation appeared first on Inside Precision Medicine.

Posted on

Epigenetic Target Could Sensitize Pancreatic Cancer to Immunotherapy

Researchers have found an epigenetic switch that pancreatic cancer cells use to protect themselves against genomic instability. In a study published in Cancer Research, the team reports that blocking the epigenetic regulator DPY30 triggered immune cell infiltration into pancreatic tumors in mice, sensitizing them to immunotherapy. 

Frequently diagnosed at advanced stages, pancreatic cancer is often resistant to conventional therapies and shows limited response to immunotherapy. This leaves patients with few effective treatment options. 

“As cancer biologists, we are intrigued by the remarkable ability of pancreatic cancer cells to tolerate genomic instability and sustained replication stress while continuing to proliferate and evade immune surveillance,” said Francesca Citron, PharmD, PhD, instructor of genomic medicine at The University of Texas MD Anderson Cancer Center and lead author of the study. “This paradox led us to investigate the adaptive mechanisms that enable cancer cells to buffer genomic instability, particularly by protecting replication forks and preventing catastrophic DNA damage.” 

The researchers were interested in finding out whether epigenetic regulators may play a direct role in safeguarding the integrity of replication forks, where DNA is copied as cells divide. Under stress, DNA replication is typically disrupted, for instance as cancer cells continue dividing and accumulating mutations that result in genomic instability. However, Citron’s team discovered that pancreatic cancer cells rely on DPY30 to protect DNA replication forks under stress and continue multiplying in spite of genomic instability. 

DPY30 belongs to a group of proteins that together form the WRAD/COMPASS complex, which is involved in epigenetics regulation. The study found that this component was able to switch the entire complex from playing a global epigenetics function to a localized role at stressed replication forks, where DPY30 stabilized.

“Historically, WRAD core components, particularly DPY30, have been primarily studied in the context of histone methylation and transcriptional regulation,” said Citron. “Our findings significantly expand this paradigm by demonstrating that these factors play a direct role in maintaining replication fork stability under conditions of stress. Importantly, we also establish a link between this mechanism and modulation of the tumor immune microenvironment, providing a conceptual bridge between replication stress and immune response.”

In a mouse model of pancreatic cancer, DPY30 inhibition destabilized replication forks, leading to increased genomic instability and activating inflammatory signaling pathways. This then triggered the recruitment of tumor-infiltrating lymphocytes and turned previously immunologically “cold” tumors into “hot” tumors that responded to immunotherapy. 

“Inhibiting DPY30 leads to increased replication-associated DNA damage, which in turn robustly enhances immune signaling pathways,” said Citron. “This dual effect, on genome stability and immune activation, opens new therapeutic opportunities to impair replication fork protection while simultaneously stimulating anti-tumor immune responses.”

Furthermore, biopsies from pancreatic cancer patients showed that higher levels of DPY30 expression were associated with higher tumor grades, a poorer prognosis and lower response rates to immunotherapy. Together, these findings point at DPY30 as both a therapeutic target and a biomarker to stratify patients who are most likely to benefit from immunotherapy. 

Going forward, the researchers plan to dive deeper into how HPY30 influences immune cell recruitment and activation within the tumor microenvironment. In parallel, they will be exploring pharmacological strategies to inhibit DPY30 and testing their efficacy in preclinical studies. Citron added: “Ultimately, our goal is to develop rational combination therapies that drive more effective and durable responses in patients.”

The post Epigenetic Target Could Sensitize Pancreatic Cancer to Immunotherapy appeared first on Inside Precision Medicine.

Posted on

Digital Twin Process Could Slash Microbial Protein Costs

A consortium of companies has developed what they call a digital twin of a microbial process to produce protein A.

Novasign, based in Vienna, hopes its participation through the ECOnti consortium will help manufacturers slash the costs of microbial proteins by improving experimental design.

According to the company, the digital twin can reduce the number of experiments needed to understand process behavior by 70% compared to Design of Experiments (DoE).

“Generally, the biggest problem in the industry right now is it’s not very efficient,” explains Mark Duerkop, PhD, CEO of Novasign.

“We need methods to learn more efficiently from experiments, design better experiments, and adapt process trajectories if something goes wrong.”

According to Duerkop, Novasign began developing an end-to-end digital twin of the full processing chain for microbial protein production as part of the ECOnti consortium three years ago.

Novasign says it develops digital twins spanning an entire process—from upstream to downstream—with the goal of improving both process development and manufacturing efficiency.

“The digital twin supports process development by systematically recommending the next set of experiments based on model-informed insights,” he says.

Setup of the Novasign ECOnti Digital Twin Technology

“During manufacturing, it can detect deviations from the intended process trajectory and support corrective actions.”

For example, if the digital twin is used to recover a process following disturbances, such as pH shifts or feed pump failure, manufacturers could significantly reduce product losses.

However, this remains for the future, he says, as the U.S. Food and Drug Administration (FDA) requires extensive validation before approving self-optimizing or autonomous manufacturing processes.

At the recent Bioprocessing Summit Europe, Duerkop presented a showcase on using the Novasign Studio software for full process control for 30 consecutive days.

He also showed how the software can use small-scale experimental data to inform scale-up and, in biosimilar development and viral vector manufacturing, can reduce experimental effort by up to 64%.

The post Digital Twin Process Could Slash Microbial Protein Costs appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Ultra- and Diafiltration Clear Leachables Effectively

In the push to de-risk biologics manufacturing, downstream purification steps are increasingly under the microscope. Now, new research led by Jonathan Bones, PhD, principal investigator in the characterization and comparability group at the National Institute for Bioprocessing Research in Dublin, and his colleagues provided compelling evidence that ultrafiltration and diafiltration (UF/DF) deliver robust clearance of process-related leachables—while also offering a predictive framework to better understand that performance.

Although UF/DF has long been assumed to reduce small-molecule contaminants, systematic data have been scarce. To address this gap, the team evaluated 28 representative organic compounds spiked into three distinct protein systems. Using liquid chromatography–high resolution mass spectrometry, they tracked how effectively these compounds were removed during UF/DF operations.

The results were striking. Twenty-four of the compounds demonstrated greater than 98% clearance across all three protein processes. Notably, variations in protein characteristics and process parameters had minimal impact on removal efficiency. Instead, clearance behavior was remarkably consistent, as reflected in similar sieving coefficients across the systems.

The intrinsic physicochemical properties of the leachables impacted clearance. Among these, lipophilicity—expressed as the octanol-water partition coefficient (Log P)—emerged as the dominant factor. Compounds with Log P values below four exhibited near-ideal clearance, while even highly hydrophobic molecules (Log P above seven) still achieved removal rates exceeding 93%. Molecular weight, polarizability, and solvent-accessible surface area also contributed to clearance outcomes.

Beyond empirical findings, the study advances the field with predictive modeling. By applying orthogonal partial least squares (OPLS) regression, the researchers developed tools capable of estimating sieving coefficients based on compound properties. These models could prove invaluable for anticipating leachable behavior without exhaustive experimental testing.

The implications are significant. As regulatory scrutiny around extractables and leachables intensifies, demonstrating effective clearance becomes central to product safety. This work not only confirms that UF/DF is a powerful mitigation step but also equips developers with quantitative tools to support risk assessments.

In an industry where unseen contaminants can pose outsized risks, the ability to both measure and predict their removal marks a meaningful step forward.

The post Ultra- and Diafiltration Clear Leachables Effectively appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

iPSC-based Manufacture vs. Autologous Model Production Costs Examined via Financial Analysis

Autologous and allogeneic cell therapies are establishing viable clinical pathways but cannot be manufactured cost-effectively at scale. Manufacturing natural killer (NK) cell therapies, and possibly T-cell therapies, using induced pluripotent stem cells (iPSCs) is understood to be significantly more cost-effective. Now those cost advantages have been quantified.

Specifically, the cost of goods per treatment can be reduced as much as 95% when manufacturing via iPSCs rather than using traditional autologous or allogenic production methods. By decoupling production from the patient, manufacturers can benefit from large-scale batch production, standardized processes, less labor, and a less complex infrastructure than either autologous or allogeneic production. Details are spelled out in a white paper by Cellistic, based on an intense cost-of-goods analysis of NK cell therapy manufacturing performed by Astrid Van Damme, PhD, head of project management at Cellistic, for her MBA thesis.

In it, Van Damme advocates creating a universal master cell bank that feeds multiple working cell banks. Those working cell banks, in turn, generate intermediate hematopoietic stem cells that are differentiated into the final therapeutic product. “This cascade creates an essentially inexhaustible, standardized source material for the entire commercial lifecycle of the product,” she asserts.

Cellistic’s internal review compared seven economic drivers for each of the three cell therapy manufacturing options. Notable advantages for an iPSC manufacturing strategy include:

  • Commercial scale production
  • Exponential scale-up or scale-out
  • Industrial-scale reproducibility
  • Use of standard cold-chain logistics
  • Minimal patient interactions
  • Reduced patient attrition
  • Potentially global market reach

An iPSC manufacturing strategy for cell therapies drops the cost of goods sold to about $5,000 per dose, down from $115,000 per dose for autologous therapeutics and $40,000 per dose for allogeneic therapeutics, Van Damme reports.

Autologous and allogeneic manufacturing, in contrast, both have severe constraints that increase costs for manufacturers and payers alike. Materials and labor alone account for 50% to 70% of autologous cell therapies—roughly $80,000 to $150,000. That’s a huge driver for U.S. list prices that, for the oncology therapeutics Kymriah® and Carvykti®, are at or above an adoption-limiting $475,000 per dose. Even after factoring in regional pricing differences and payer discounts, the net per-dose costs to payers are still extremely high.

Compared to iPSC manufacturing at clinical scale (150 vials and 200 M cells per vial) and at commercial scale (450 vials with 400 M cells per vial), Van Damme indicates:

  • Labor costs constituted about 13% of the costs of goods (vs. about 70% for autologous methods)
  • Costs per vial drop approximately 40%
  • Fixed costs were diluted by a factor of three

“Once a minimum threshold of operational maturity and throughput is achieved, iPSC-based manufacturing economics become comparatively robust to routine operational variability,” the paper concludes.

The post iPSC-based Manufacture vs. Autologous Model Production Costs Examined via Financial Analysis appeared first on GEN – Genetic Engineering and Biotechnology News.