Radically different
Baxter International disclosed how much it paid its new CEO last year in a recent filing with the U.S. Securities and Exchange Commission. The medical device manufacturer also disclosed pay packages for other current and former executives — including a severance payment for its former CEO — and reported higher pay for its median employee. Baxter’s…
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Researchers at the University of Houston, working with collaborators at Baylor College of Medicine and The University of Texas MD Anderson Cancer Center, have identified a mechanism that identifies epithelial cell stress as a one of the main drivers of Crohn’s disease, a finding that runs counter to much current thinking of Crohn’s disease as immune-mediated and instead frames it as a failure of within the intestinal barrier. The study, published in Gastro Hep Advances, shows that chronic integrated stress response (ISR) activation and a related cell death pathway, necroptosis, form a feedback loop that damages intestinal epithelial cells and prevents cell regeneration leading to sustained inflammation.
“It’s a paradigm shift from the way we’ve thought about the disease,” said senior author Seema Khurana, PhD, a professor of biology and biochemistry at the University of Houston. “Existing therapies primarily manage symptoms because we don’t know what causes the disease. We believe our research brings us closer to identifying those drivers.”
Crohn’s disease is typically treated with anti-inflammatory therapies aimed at suppressing immune activity, but only a minority of patients have long lasting benefits. This current study may help explain why anti-inflammatories only have limited benefits by showing that intestinal barrier dysfunction is not simply a consequence of inflammation but is a factor in disease development.
For their research, the team sought to discover how stress signaling within certain epithelial cells contribute to disease progression. The ISR is a conserved cellular pathway that helps cells respond to stress by temporarily reducing protein production and activating processes that restore cellular balance, including stress-response gene expression, protein quality control, and metabolic adaptation. While short-term ISR activation is a temporary response to cellular stress, the researchers found that in Crohn’s disease, ISR signaling becomes chronically activated.
“Our results identify ISR activation as a unifying hallmark of epithelial stress in CD, regardless of whether the initiating insult is intrinsic (loss of villin-1/gelsolin) or extrinsic (TNF-α dysregulation),” the researchers wrote.
The result of this chronic ISR activation is that instead of helping epithelial cells become healthy, they are instead kept in a dysfunctional state. This leads to mitochondrial stress and triggers necroptosis, a form of programmed cell death that releases inflammatory signals. The combination of ongoing stress signaling and cell death prevents epithelial regeneration and weakens the intestinal barrier, allowing microbes to infiltration tissue in the intestine further increasing inflammation.
Prior studies have focused on this form of dysfunction to Crohn’s disease, but ISR activation had not been clearly characterized as a central driver of disease development. To address this, the team used a number of different models of Crohn’s disease, including genetically engineered mice with epithelial-specific ISR activation, mice with chronic inflammation driven by TNF-α dysregulation, and patient-derived intestinal organoids. The organoids allowed the researchers to directly study human epithelial responses.
The resulting data showed that for all the models, the same pattern of chronic ISR activation, increased necroptosis, impaired epithelial survival, and failure of regenerative growth emerged.
To begin finding potential therapeutic approaches based on these new findings, the investigators then tested whether blocking these pathways could reverse intestinal damage. Using both experimental inhibitors and two FDA-approved cancer drugs, pazopanib and ponatinib, repurposed at low concentrations, they were able to suppress ISR signaling and necroptosis. This restored epithelial cell survival, improved regeneration, and reestablished barrier integrity.
“A major advance of this work is the demonstration that pharmacologic inhibition of ISR or necroptosis restores epithelial homeostasis by promoting regenerative growth of the epithelium in both murine and human models of CD,” the researchers wrote.
If additional studies can establish ISR inhibition as safe and effective for human use, this research could be the beginning of a shift in how Crohn’s disease is treated. Instead of focusing only on controlling inflammation, a new class of treatments could aim to repair the epithelial barrier directly. This approach aligns with emerging evidence that permeability barrier healing is a stronger predictor of long-term remission than traditional measures such as mucosal healing.
Further, because both pazopanib and ponatinib are already approved drugs that are known to be safe and have well characterized pharmacology profiles, the path to these new treatments could be on a fast track.
“If you had to start from scratch to identify and develop a drug, it takes 10 to 15 years and can cost between $1 billion to $2 billion,” Khurana said. “For a patient who is suffering from chronic Crohn’s disease, they’re looking for some immediate relief. Our goal was to make our findings much more translatable to real patients.”
Beyond drug development, the study points to new opportunities for improving clinical care. Biomarkers of ISR activation, such as phosphorylated eIF2α or RIPK3 expression, could help identify patients with barrier dysfunction and guide treatment decisions. Patient-derived organoid systems may also enable personalized testing of therapeutic responses before treatment.
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WASHINGTON — The Food and Drug Administration on Tuesday announced efforts to make clinical trials more efficient, starting by reviewing data in real time from trials conducted by AstraZeneca and Amgen.
The agency also asked the public to weigh in on a potential pilot program to work with companies that use AI to enhance safety monitoring and medication dose selections, identify safety signals, and improve patient recruitment in clinical trials.
AstraZeneca is conducting a Phase 2 trial of its combination therapy for patients with an aggressive form of lymphoma. The trial will take place at the University of Texas MD Anderson Cancer Center and the University of Pennsylvania. Amgen is conducting a Phase 1b trial of its treatment for small cell lung carcinoma. The trials will rely on a real-time data platform built by Paradigm Health.
What happens when the scalability and redosability of messenger RNA (mRNA) is combined with the durability and programmability of gene therapy?
According to Serif Biomedicines, a five-year-old startup that emerged from stealth mode this month, the result is “modified DNA,” a new class of therapeutics designed to be programmable, durable, scalable, and redosable—while minimizing the drawbacks of both mRNA and gene therapy.
Modified DNA builds upon generative protein and mRNA platforms created by Flagship Pioneering, the venture capital giant which founded Serif in 2021. On April 21, Flagship formally launched Serif with an initial commitment of $50 million in financing—capital that Serif intends to use toward developing its scalable platform for optimizing and manufacturing Modified DNA treatments, aided by artificial intelligence (AI), and advancing its first drug discovery programs.
“The reason we’re bringing the company out of stealth mode now is we think we have made progress. We’ve made real progress that we’re excited to share with the world, that we’re excited to get feedback from the broader scientific community on, and we want to tell that story more broadly,” Jacob (Jake) Rubens, PhD, Serif’s co-founder and CEO, and an Origination Partner at Flagship Pioneering, told GEN.
“It’s been on our minds for a long time: What might be possible when DNA becomes an engineerable biotechnology for the first time?”
It’s a question pursued by numerous researchers and companies over the years as they sought to capitalize on DNA’s qualities of being a durably expressing molecule capable of coding for any gene, producing proteins or RNAs in a cell-specific way, as well as being scalable to manufacture and capable of re-dosing for patients.
“Those are, I think, the key differentiating attributes of theoretical DNA medicines. So the question for us became not, would this be valuable if we could do it, but why hasn’t anyone done it yet?” Rubens explained. “We’ve known about the centrality of DNA in biology, the central information molecule in DNA. We’ve known this for 75 years since Watson and Crick’s seminal discoveries around how the structure of DNA enabled it to function as an information molecule.”
“And when we looked at this space,” he continued, “we saw that there were two key problems: The first is that DNA is a highly inflammatory molecule. The second is that DNA needs to be delivered not just into a cell, but into the nucleus, the center of the cell.”
To create Modified DNA, Serif alters the structural and chemical form of DNA in order to minimize innate immunogenicity as lipid nanoparticles drop off the DNA not in the nucleus, but in the cytoplasm of the cell.
Once inside the cell nucleus, Modified DNA reverts to unmodified DNA, enabling transcription into therapeutic RNA and proteins. The resulting treatments are designed to last longer, be given more than once, and be programmed for cell-specific expression. To enhance durability, Serif delivers with its Modified DNA proteins which help the DNA access the nucleus. The proteins, called mRNA co-factors, are designed to transiently express proteins that enhance entry into the nucleus and gene expression.
Pending an announcement it expects to make later this year, Serif isn’t revealing specifics of its initial drug discovery programs, except to say that they focus on rare diseases and immune programming.
“This is not meant to be a limited list of where we could go but the areas that we think we’re going to go first, which are likely in addressing protein deficiencies in genetic diseases,” Rubens said.
Modified DNA has shown itself to be disease agnostic, he added, reflecting DNA’s qualities as a general, programmable information molecule: “One of the reasons we’re so excited about, the future of modified DNA as a new biotechnology akin to RNA, akin to protein, is its centrality in biology. It is the fundamental information molecule inside of all of us, inside of every living thing on this planet. So that is really the existence proof that it is generalizable.”
Also later this year, Serif plans to present data at an as-yet-unspecified scientific conference that will show modified DNA’s tolerability in non-human primates, as well as sustained gene expression with therapeutic effects in preclinical models following intravenous (IV) administration.
Serif aims to transform Modified DNA into treatments as effectively and commercially successfully as Amgen, Genentech (now a member of the Roche Group), and later Regeneron did with engineered proteins, as Alnylam Pharmaceuticals did with small interfering RNA (siRNA), and as Moderna more recently accomplished with mRNA—most notably in developing its SpikeVax® COVID-19 vaccine, which the FDA authorized for emergency use in 2020 and fully approved in 2022.
Flagship launched Moderna in 2010; the company went public in 2018 by raising $604 million, the largest-ever U.S. biotech initial public offering (IPO) until Kailera Therapeutics raised $625 million earlier this month.
At Flagship, Rubens is a scientist entrepreneur who leads the firm’s Pioneering Business Unit, which establishes and grows companies based on new biotechnology. In addition to Serif, Rubens co-founded Quotient Therapeutics, which develops therapies based on its somatic genomics platform; Tessera Therapeutics, which writes therapeutic messages into the genome through a genome engineering approach called GeneWriting
; and Sana Biotechnology, a developer of treatments based on engineered cells. He also launched Kaleido Biosciences, a microbiome therapeutics company that ceased operations in 2022.
Before joining Flagship, Jake received his PhD in microbiology from MIT, working with Tim Lu, MD, PhD, a core member of the Synthetic Biology Center, through the support of a National Science Foundation Graduate Research Fellowship. At MIT, Jake helped enable “intelligent” cell therapies by inventing gene circuits that allow engineered cells to do novel analog, digital, and hybrid computations.
Based in Cambridge, MA, Serif employs about 50 people and as of Wednesday was disclosing five open positions on its website in its three areas of focus: Chemistry (associate scientist and senior scientist, both specializing in LNP formulations), Molecular Biology (research associate and senior scientist), and Research/Discovery (scientist specializing in bioanalytical assays).
“I’m not at this point going to provide any guidance on how much more we will or won’t grow,” Rubens said. “We’re quite agile and responsive to the company’s needs.”
The post ‘Type’ Casting: Flagship-Founded Serif Modifying DNA into New Therapy Class appeared first on GEN – Genetic Engineering and Biotechnology News.
The video starts simply: a couple at home, music playing, dogs in the background. Allison Barry smiles as she talks about the rhythms of her life with her husband Chris, how they’ve built a life together that’s carefully planned, structured, and anchored around work and the future. Vacations could be put off. Retirement would be the time to explore.
Barry loved her job. As senior director of portfolio communications at Exact Sciences, she was deeply involved with the launch of Cancerguard, a new multi-cancer early detection (MCED) test. The day that Cancerguard became available, September 10, 2025, would be a day to remember. “We were in New York at the New York Stock Exchange, and [the announcement of Cancerguard] was on the big billboard,” said Barry in the video released by Exact Sciences a month ago. “It was one of the proudest moments of my entire life.”
But that wasn’t the only notable event of the day. Barry did one other thing—she ordered the Cancerguard test, expecting a negative result. Then the tone in the video shifts. Barry’s test was positive. “She was the very first positive result,” Tom Beer, MD, then chief medical officer (CMO) at Exact Sciences, told me as we watched the video about Barry’s experience with Cancerguard. “She literally ordered it the first day.”
What follows is a blur of scans, fear, and uncertainty until doctors find a tumor the size of a football (22 cm). The diagnosis: stage-one mucinous ovarian cancer, a disease that is almost always caught too late. Surgery follows. The outcome is positive. That all happened in the span of six months. Today, Barry is cancer-free.
Beer and the team at Exact Sciences have spent years designing Cancerguard, named in the same vein as the company’s flagship product Cologuard, to identify cancers that currently lack effective screening options and to catch them earlier, when treatment is more likely to succeed.
Cancerguard is a multi-biomarker MCED classifier that combines two types of biological signals: cell-free DNA (cfDNA) methylation and protein biomarkers. Each is analyzed separately, then integrated into a single result. If either signal is positive, the test flags a potential cancer. “They’re complementary sources of information,” Beer explained.
Beer’s colleague Frank Dielh, PhD, presented new data during the AACR 2026 conference showing that the multi-biomarker MCED approach used in the Cancerguard test improves cancer detection across stages by combining these two signals, with each set of biomarkers contributing independently to overall performance.
The prospective case-control study of 3,163 participants showed detection was driven by cfDNA methylation alone in 47.1% of cases, protein alone in 7.4%, and both in 45.5%, with no false positives showing both markers, underscoring the value of a multi-signal approach for earlier and broader detection.
But what’s most valuable, according to Beer, is the stages that the combined scores provide. Across a broad range of cancers, sensitivity increases from about 24% in stage one to 90% in stage four. While those early-stage numbers may seem modest at first glance, Beer emphasized the context. “We’ve been really focused on early-stage sensitivity as our North Star,” said Beer. “We’re screening for cancers that currently have zero effective screening. So, even incremental sensitivity is meaningful.”
By layering different biological signals, the test builds a more complete picture: one that is particularly valuable when tumors are small and harder to detect.
In November 2025, a couple months after Cancerguard launched, Exact Sciences made a deal to be acquired by Abbott, a major bet for the medical device and healthcare company on cancer diagnostics. While the technology for Cologuard and Cancerguard was already in development at Exact, the scale of deployment changes dramatically with access to a global healthcare network. “Abbott has a truly global presence,” Beer said. “Relationships with health systems and governments around the world. That changes how we think about opportunity.” An ongoing study in Japan reflects that shift.
On December 11, 2025, Exact Sciences launched the CRANE (Cancer Recognition and Assessment through Non-invasive Evaluation) Study in Japan—a large, multi-center trial enrolling about 2,000 participants—to evaluate the sensitivity and specificity of Cancerguard test across different cancer types and stages. “If you’re going to build something for global use, you need to understand how it behaves globally,” he said. “Geography and ethnicity could influence performance.”
Designing a cancer screening test isn’t just about detecting as many cases as possible. It’s about balance, particularly between sensitivity and specificity. Internally, Beer explains, the team models outcomes in terms of life-years gained versus the risks and costs of false positives. These trade-offs determine where thresholds are set within the algorithm. “We’re not just picking a random cutoff,” he said. “We’re thinking deeply about how to deliver the greatest public health impact.”
These internal models, though not publicly shared, guide every stage of development. The goal is not just accuracy but meaningful outcomes, catching cancers early without overwhelming patients and healthcare systems with unnecessary follow-ups.
For all the technical detail, our conversation keeps returning to people. Beer recalls another friend who retired at 65, only to be diagnosed with advanced pancreatic cancer six months later. He didn’t survive.
Placed alongside Barry’s story, the contrast is stark. One life was altered by early detection; the other never got the chance to do anything about it. What makes Barry’s story powerful is not just its outcome but also its implication, which is that cases of cancer can be caught early enough to change everything. The ultimate goal for Beer is to make such stories routine.
The post Multi-Cancer Early Detection Goes Global and Gets Personal appeared first on Inside Precision Medicine.
After a yearslong legal feud, Elon Musk and OpenAI CEO Sam Altman are heading to trial this week in Northern California in a case that could have sweeping consequences. Ahead of OpenAI’s highly anticipated IPO, the court could rule on whether the company is allowed to exist as a for-profit enterprise and might even oust its current executive leadership, including Altman.
Musk is suing OpenAI, alleging that Altman and OpenAI president Greg Brockman deceived him into bankrolling the company in its early days by promising to maintain it as a nonprofit dedicated to developing AI that benefits humanity, only to later restructure the company to operate a for-profit subsidiary. Musk cofounded OpenAI with Altman and others in 2015, but he left in 2018 after a bitter power struggle.
Musk is seeking as much as $134 billion in damages from OpenAI and Microsoft, one of OpenAI’s biggest financial backers. He is also asking the court to remove Altman and Brockman from their roles and to restore OpenAI as a nonprofit. Musk has asked the court to award any damages to OpenAI’s nonprofit rather than to him personally.
Nine jurors will deliver an advisory verdict, a non-binding recommendation, to guide the judge in deciding Musk’s claims against Altman. Musk, Altman, and Brockman will take the stand. Former OpenAI chief scientist Ilya Sutskever, former OpenAI CTO Mira Murati, and Microsoft CEO Satya Nadella are also expected to testify. Cringey texts, raw diary entries, and endless scheming behind the founding and growth of OpenAI are expected to come to light.
In an industry enveloped in secrecy, the trial will be a rare opportunity for the public to look behind the curtain and find out what’s going on in the companies creating the most transformative technology ever built.
When OpenAI was originally founded as a nonprofit, backed by a $38 million donation from Musk, the company vowed to create open-source technology for the public’s benefit, unconstrained by a need to generate financial returns. But over the years, the company began to claim that intensifying competition could make it dangerous to share how it develops its AI models and that a nonprofit structure could not raise enough money to keep building AI. (MIT Technology Review was first to report on OpenAI’s internal conflicts around its mission.)
The court has already found that in 2017 Altman and Brockman wanted to establish a for-profit arm, while Musk proposed merging OpenAI with his electric-car company, Tesla. When Musk threatened to stop funding, Altman and Brockman told him that they were committed to keeping the company a nonprofit. Musk alleges that they pursued plans to pivot to a for-profit without informing him. According to OpenAI, Musk agreed that the company needed a for-profit entity and even wanted to be its CEO.
But even if Musk proves he was duped by Altman and Brockman, he may not have standing in the first place to sue them for restructuring the company to operate a for-profit subsidiary. Some legal scholars are puzzled over why the judge allowed him to bring this claim. “The idea that Elon Musk can sue because he was a donor or used to be on the board is pretty puzzling,” says Jill Horwitz, a law professor who studies nonprofit law at Northwestern University. “Typically, it’s up to the attorneys general to bring such a claim to enforce the charitable purposes. And that’s already happened.”
In October 2025, state attorneys general of California, where OpenAI is headquartered, and Delaware, where OpenAI is incorporated, struck a deal with OpenAI to approve its new corporate structure on a series of conditions. For example, a safety and security committee at the nonprofit would review safety-related decisions made by the for-profit subsidiary. Critics of the restructuring, including Musk, AI safety advocates, and civil society groups, have tried to stop it.
California’s attorney general has declined to join Musk’s lawsuit, saying that the office did not see how his action serves the public interest.
Still, whether the deal holds OpenAI to its nonprofit mission is an open question. “Elon Musk should have to show … what the deficiencies are in what’s been agreed to by OpenAI with the attorneys general,” says Rose Chan Loui, the director of the UCLA School of Law’s philanthropy and nonprofit program. Even with the terms in place, holding OpenAI to them depends on “how much they can enforce it and how much transparency they get into OpenAI’s work.”
More importantly, legal experts say the case is being considered under the wrong body of law. Musk argues that Altman and Brockman breached OpenAI’s charitable trust by creating a closed-source, for-profit subsidiary. As a result, the court has been analyzing the claim under the law of trusts. “But OpenAI is not a trust. OpenAI is a corporation. And so really they should be looking at … the law of charitable nonprofit organizations,” says Chan Loui.
Despite all the legal muddiness, the outcome of the trial could upend the AI race. Any one of the remedies that Musk seeks could cripple OpenAI as it races to go public by the end of the year. OpenAI, which is valued at over $850 billion, has described the litigation with Musk as a potential risk to its business. Musk’s rival company xAI, which makes the chatbot Grok, is expected to go public as a part of his rocket company SpaceX as early as June. If Musk prevails, xAI, which in combination with SpaceX is valued at $1.25 trillion, could get a big advantage in the AI race.
And the trial has helped expose the bitter schism between Musk and the company he once helped to found. An OpenAI spokesperson referred MIT Technology Review to a post on X: “This lawsuit has always been a baseless and jealous bid to derail a competitor.” Although Musk’s lawyers did not immediately respond to a request for comment, he has posted on X that “Scam Altman lies as easily as he breathes.”
MIT Technology Review will have ongoing coverage of Musk v. Altman until its conclusion. Follow @techreview or @michelletomkim on X for up-to-the-minute reporting.
A new U.S. policy that recommends offering hepatitis B vaccine at birth only to babies perceived to be at risk of neonatal infection will lead to increased numbers of infected infants and more cases of chronic hepatitis B infection in children that will generate millions of extra dollars in health care costs, two studies published Monday project.
“Avoiding an increase in neonatal infections under the targeted recommendation would require historically unattained levels of maternal [hepatitis B] screening or birth-dose coverage among infants of unscreened mothers,” said one of the studies, from researchers at Boston University, the University of Florida, and Johns Hopkins University.