Tag: Academic research

Posted on

StockWatch: Abivax Survives a Roller Coaster Week

More acutely than most companies, Abivax (Euronext Paris and Nasdaq: ABVX) felt firsthand the ups and downs of the proverbial stock market roller coaster this past week as investor fears over safety signals associated with the French biotech’s late-stage ulcerative colitis (UC) drug candidate briefly overshadowed its positive Phase III clinical results.

Shares of Abivax skidded on June 2, the first trading day after the company announced positive topline results from the Phase III ABTECT maintenance trial (NCT05535946), which is assessing obefazimod in adults with moderately to severely active UC.

Abivax’s stock plummeted after analysts from Jefferies, Morgan Stanley, Truist Securities, and Wedbush Securities raised as a safety concern a portion of data showing malignancies in nine patients among the 580 enrolled in the study. Jefferies reacted the strongest among the firms, downgrading Abivax’s stock rating from “Buy” to “Hold” and lowering its 12-month price target on the company’s shares 44%, from $160 to $90.

“Cancer signal complicates matters,” Faisal Khurshid, a managing director and equity research analyst with Jefferies, wrote in a research note. “Promise of the drug is to deliver strong efficacy w/ oral convenience and w/out JAK safety baggage. However, cancer cases seen in maintenance break our thesis. Even if proven to be not drug-related or v[ery] low incidence, we expect an overhang to investor interest, strategic optionality, and commercial uptake.”

Wedbush analyst David Nierengarten upgraded Abivax on the overall ABTECT data, from “Underperform” to “Neutral,” though he lowered the firm’s target price 18%, from $110 to $90. But he also cautioned, according to published reports, that the data increase the risk of obefazimod being approved with a black box warning on its label.

The other two firms lowered their price targets as well:

  • Morgan Stanley (Judah Frommer)—Down 9% from $145 to $132, maintaining its “Overweight” rating.
  • Truist (Greg Renza)—Down 4% from $140 to $135, maintaining its “Buy” rating.

Of the nine patients diagnosed with malignancies, seven received the higher 50 mg dosage of obefazimod, one the lower 25 mg dose, and one placebo. Squamous cell carcinoma cases were seen in three of the patients—one dosed at 25 mg, the others 50 mg. Basal cell carcinoma cases emerged in two 50 mg patients and one placebo patient, while cases of prostate cancer, breast cancer, and colonic dysplasia were seen in one patient each, all dosed at 50 mg.

In its announcement of the ABTECT data, Abivax stated that the prostate, breast, and colon cancer cases “were considered unrelated to treatment by investigators.” Among the squamous cell and basal cell cases, two of the four 50 mg patients were deemed “not/unlikely related to drug,” while of the remaining two cases, one had a medical history of skin cancer, the company added.

Swinging negative, then positive

Yet the cancer and pre-cancerous cell cases nevertheless led investors to sell off their Abivax shares on June 2. Abivax’s ordinary shares traded on Euronext Paris plummeted 44% from €111.80 ($128.81) to €63.10 ($72.70), while the company’s American depositary shares (ADSs) traded on the Nasdaq Global Market also plunged 44% from $129.69 to $72.50.

No sooner did Abivax shares start to free-fall, however, than a more positive narrative emerged among another set of analysts. They cited the ABTECT maintenance study’s overall positive findings, which showed that both doses of the first-in-class miR-124 enhancer met the study’s primary endpoint by showing positive absolute clinical remission rates of 50.8% for the 25 mg dose and 51.3% for the 50 mg dose. Both results blew away the 10.4% absolute clinical remission rate of placebo.

When adjusted for placebo, obefazimod showed placebo-adjusted clinical remission rates of ∆39.3% for the 25 mg dose and ∆40.3% for the 50 mg (both p<0.0001).

Obefazimod also met all of ABTECT’s key secondary endpoints, including endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement  (HEMI), corticosteroid free clinical remission, and sustained clinical remission.

In endoscopic remission, Abivax showed in an investor presentation, obefazimod showed placebo-adjusted endoscopic remission rates of 38% (50 mg) and 31% (25 mg), outperforming nine marketed drugs that carry indications in UC—which ranged from 8% by both Omvoh® (mirikizumab-mrkz) marketed by Eli Lilly (NYSE: LLY) and  Skyrizi® (risankizumab-rzaa) marketed by AbbVie (NYSE: ABBV), to 20% shown by AbbVie’s Rinvoq® (upadacitinib), Tremfya® (guselkumab) marketed by Johnson & Johnson (NYSE: JNJ), and Velsipity® (etrasimod) marketed by Pfizer (NYSE: PFE).

“While most therapies cluster in the 8% to 20% range, obefazimod stands alone at 31% and 38%, demonstrating a level of efficacy that is well beyond the range achieved by other treatment classes. This finding is particularly important because achieving endoscopic remission has been consistently associated with lower relapse rates and better long-term patient outcomes,” Abivax CEO Marc de Garidel said June 1, addressing analysts during a conference call held to discuss the ABTECT study results.

He also cited Abivax’s Phase IIa/IIb open-label extension study (NCT05177835), designed to assess the long-term safety and the efficacy profile of 25 mg obefazimod given once daily in subjects previously enrolled in two earlier Phase II trials, ABX464-102 (NCT03368118) or ABX464-104 (NCT04023396). Data from the extension study announced in May showed that patients receiving 50 mg of obefazimod for two to four years and then transitioned to 25 mg for up to an additional three years maintained durable clinical remission and a favorable safety profile for up to seven years of treatment exposure.

Abivax said it plans to submit a New Drug Application (NDA) submission to the FDA for obefazimod late in the fourth quarter.

“Transformational potential”

“Taken together, we believe these results validate the transformational potential of obefazimod and position us well as we advance toward our planned NDA submission in late 2026,” de Garidel said, declaring: “Today’s results firmly establish obefazimod as a potential new standard of care for the treatment of ulcerative colitis.”

Thomas J. Smith, senior managing director, immunology and metabolism, and a senior research analyst with Leerink Partners, appeared to agree with de Garidel in a research note.

“We believe obe[fazimod]’s results suggest a best-in-disease maintenance profile, especially among oral therapeutics in UC,” Smith wrote in his initial research note on Abivax’s ABTECT data. “We continue to believe that obe features the most compelling late-stage clinical profile for a novel oral agent in IBD [inflammatory bowel disease] amid heightened M&A/BD [business development] activity that underscores large pharma’s interest in the space.”

Several big-money merger-and-acquisition (M&A) deals in recent years have centered around pharma giants buying developers of drugs for UC, Crohn’s disease, and other forms of IBD. The biggest of these was Merck & Co. (NYSE: MRK) acquiring Prometheus Biosciences for $10.8 billion in 2023, while Lilly bought out Morphic Therapeutic for about $3.2 billion in 2024; Roche Holding (SIX Swiss Exchange: ROP and RO; OTCQX: RHHBY) snapped up Telavant Holdings for up-to-$7.25 billion in 2023; and Pfizer acquired Arena Pharmaceuticals for $6.7 billion in a deal completed in 2022.

Abivax itself has found itself rumored as a potential candidate for being acquired—it made GEN’s A-List of Top 10 Takeover Targets of 2026—since last summer, when the company reported dazzling data from two Phase III trials, ABTECT-1 (ABX464-105; NCT05507203) and ABTECT-2 (ABX464-106; NCT05507216).

As for the reported malignancies, Smith commented in a follow-up research note: “We do not view the reported malignancies as an outsized or approvability-limiting safety risk, particularly given the absolute low event counts, investigator assessment that the non-NMSC malignancies were unrelated to treatment, IDMC [independent data monitoring commission] adjudication supporting the safety profile, lack of organ-specific clustering, and mitigating circumstances noted across each case.”

Obefazimod is a small molecule upregulator of miR-124, an anti-inflammatory microRNA. It enhances the selective splicing of a single long noncoding RNA to generate miR-124, which downregulates cytokines and chemokines shown to promote inflammation, including tumor necrosis factor (TNF) alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1), and IL-17, as well as Th17+ cells.

Under its former name ABX464, obefazimod was initially developed against HIV but was repurposed to fight inflammatory conditions based on its anti-inflammatory effect.

“Best in indication”

Also bullish on Abivax is Citizens JMP Securities, where Jason Butler, managing director, biotechnology equity research, raised his firm’s price target 43%, from $131 to $187, based on ABTECT’s positive data exceeding expectations. Butler maintained Citizens JMP’s “Market Outperform” rating on Abivax shares.

“We view efficacy (~40% placebo-adjusted clinical remission rate) as best in indication, easily surpassing drugs across all approved classes of UC therapies,” Butler wrote. “We believe the Phase [III] efficacy and safety results, together with its oral once-daily profile, support that obefazimod can be transformational to the UC treatment landscape, benefiting both earlier-stage and more severe/refractory patients.”

“Importantly, we also view the safety profile as compelling and are comfortable that the drug is not associated with a clear malignancy risk (which is the primary debate driving stock volatility post-market),” Butler added.

The more positive feedback from analysts apparently swayed investors, as Abivax’s stock price rebounded roughly 40% on both exchanges since the initial nosedive. The Nasdaq shares vaulted 24% to $90.15 on Wednesday, then rose another 16% to $104.93 Thursday before dipping 3% Friday, finishing the week at $101.53 and with a 23.5% five-day decline.

On Euronext Paris, Abivax shares bounced back 13% to €71.25 ($82.09) on Wednesday, jumped another 18% Thursday to €83.95 ($96.72), then finished Friday up 5% to €87.85 ($101.21) and a 22.5% five-day decline.

Butler said the maintenance study’s data suggested that Abivax could potentially generate more positive clinical results for obefazimod in its ongoing Phase IIb ENHANCE-CD induction trial in Crohn’s disease (NCT06456593), which is expected to read out in mid-2027. He added that ABTECT’s results were strong enough to support approval of both the 25 mg and 50 mg doses: “While we anticipate malignancies to be included in the label, we continue to believe in the differentiated profile of obefazimod.”

Speaking with analysts, de Garidel agreed with pursuing approvals for obefazimod at both 25 mg and 50 mg: “Our thinking is that both doses will be very helpful for patients, and we plan to file at year-end with those two doses for maintenance.”

Leaders and laggards

  • Absci (Nasdaq: ABSI) shares climbed 24% from $5.94 to $7.34 Thursday after Leerink Partners initiated coverage of the generative AI-based drug developer with an “Outperform” rating and a 12-month price target of $12. Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink, lauded the company’s drug mechanism of blocking prolactin (PRL)–prolactin receptor (PRLR) signaling as seen in its lead pipeline candidate ABS-201, an anti-prolactin receptor antibody in Phase I/II studies for androgenetic alopecia that advanced into the clinic last year, with a Phase II study in endometriosis expected to start in the fourth quarter: “We see a totality of evidence supporting PRLR blockade in these indications, and see even partial/early clinical validation opening a clear path to valuation >double the current market cap (~$1.1B fully diluted),” Foroohar wrote in a research note.
  • Fulcrum Therapeutics (Nasdaq: FULC) shares jumped 9.5% from $3.37 to $3.69 Friday after the developer of small molecule drugs for rare blood disorders disclosed in a regulatory filing that it will slash its workforce approximately 85%—from 57 to nine full-time employees—in a cost-cutting move expected to be substantially completed during the second quarter. Fulcrum said it expects to incur approximately $4.2 million in charges related to the layoffs, consisting primarily of employee severance, employee benefits, and related costs. Fulcrum vowed to “significantly” reduce its operating expenses and launched a strategic review after scrapping its lead pipeline program to develop pociredir as a treatment for sickle cell disease (SCD). The development followed the FDA expressing heightened concerns about pociredir’s risks and benefits in fighting SCD due to an unexpectedly high rate of secondary blood cancers seen with another PRC2 inhibitor, Tazverik®(tazemetostat), marketed by Ipsen (Euronext Paris: IPN).
  • Oculis Holding (Nasdaq: OCS) shares tumbled 36% from $22.70 to $14.51 June 1, after the Swiss neuroophthalmology and ophthalmology drug developer said it did not plan to pursue an FDA filing seeking approval for its OCS-01 eye drops in diabetic macular edema (DME). Oculis acknowledged that OCS-01 failed two Phase III trials, DIAMOND-1 (NCT05066997) and DIAMOND-2 (NCT06172257), by missing their primary endpoint, mean change in best corrected visual acuity early treatment diabetic retinopathy study (BCVA ETDRS) letter score at Week 52. The key secondary endpoint of the proportion of patients with ≥15-letter gain in BCVA was not met in both trials, though another secondary endpoint, retinal thickness as measured by OCT, showed a “substantial and persistent” reduction with OCS-01 vs vehicle at all visits in DIAMOND-2, and at all visits except Week 52 in DIAMOND-1.

The post StockWatch: Abivax Survives a Roller Coaster Week appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

STAT+: Lilly shares safety, tolerability data on its next-gen obesity drug

Eli Lilly has already established that its next-generation obesity drug can lead to highly rapid weight loss. Researchers disclosed new data Saturday that provide more details on the safety and tolerability of the closely-watched therapy.

Lilly previously said that in one late-stage study, called TRANSCEND-T2D-1, retatrutide helped people with diabetes lower blood sugar and lose a significant amount of weight, which is notable since those who have diabetes tend to lose less weight on treatment than those who don’t.

New data showed that seven out of the 403 participants who received retatrutide experienced arrhythmias (irregular heart beats), and three treated participants experienced major cardiovascular complications, compared with none in the placebo group. The data were presented at the annual meeting of the American Diabetes Association and published in the Lancet.

Continue to STAT+ to read the full story…

Posted on

GLP-1 Drugs Lower Risk of Death by 44% in Obesity and Autoimmune Disease

An analysis of electronic health records from over 26,000 adults with obesity and at least one autoimmune disease has shown that those taking GLP-1 medication experienced fewer cardiac events, were less likely to visit the ER, and had a lower risk of death. These findings were published today in the Journal of the American Heart Association and presented at the American Diabetes Association 2026 Scientific Sessions in New Orleans. 

“This is a high-risk population, and historically we’ve had limited data to guide treatment decisions,” said Amy Sheer, MD, associate professor of medicine and director of the Obesity Medicine Fellowship program at the University of Florida. “In this real-world analysis, we found a consistent signal toward fewer serious complications including blood clots and lower mortality among patients treated with GLP-1 receptor agonists. For people who are overweight or living with obesity and an autoimmune disease, this study offers a hopeful signal that medications already in use today may be beneficial in reducing their risk of cardiovascular disease.”

GLP-1 receptor agonists are commonly prescribed drugs to help patients with type 2 diabetes lose weight and manage their blood sugar levels. This study is the first to examine the potential cardiovascular benefits of these drugs in a high-risk population of patients with both obesity and an autoimmune disease—both of which are associated with a higher risk of cardiovascular and blood clot events. 

Sheer and colleagues reviewed electronic health record data from 26,408 adults treated in the OneFlorida+ network from 2014 to 2024, covering 14 healthcare organizations across Florida, Georgia, and Alabama. Half of the patients were taking GLP-1 drugs over this 10 year period, while the other half did not. 

Across this population, GLP-1 treatment was found to reduce the risk of blood clots by 17%, of pulmonary embolism by 31%, and of death by 44%. Visits to the emergency department were also lowered by 21%, and a modest decrease in stroke risk of 13% was also found. 

“The 44% reduction in all-cause mortality observed among patients with obesity and co-occurring autoimmune disease is a striking finding that demands our attention,” said Fatima Cody Stanford, MD, associate professor of medicine and pediatrics at Harvard Medical School, who was not involved in the study. “As an obesity medicine physician scientist who regularly cares for patients with complex inflammatory conditions, this study reinforces what many of us have suspected clinically—that the benefits of GLP-1 receptor agonists extend well beyond blood sugar control and weight loss and may fundamentally alter the disease trajectory for some of our highest-risk patients.”

Although this study cannot prove a causal link between GLP-1 medication and the effects seen on the patients taking them, it opens the door to future combinations of treatments for autoimmune disease with GLP-1 drugs. More research is still needed to understand the role this medication could play as a potential preventive therapy for high-risk patients.

“Our research broadens the conversation around GLP-1 receptor agonists,” said Sheer. “For clinicians, we hope these findings may prompt a more thoughtful, individualized approach when considering these therapies in higher-risk patients who have both obesity and autoimmune disease.”

The post GLP-1 Drugs Lower Risk of Death by 44% in Obesity and Autoimmune Disease appeared first on Inside Precision Medicine.

Posted on

STAT+: Detailed data show Pfizer’s monthly obesity drug continues to show potential

Detailed data from a mid-stage study offered further evidence that the obesity drug Pfizer acquired from the biotech Metsera could be dosed monthly. But it’s not clear how competitive the treatment would be against weekly injectables on the market and in development that may lead to greater weight loss.

In the study, called VESPER-3, patients with obesity took weekly doses of the drug, called berobenatide, for 12 weeks and then transitioned to higher monthly doses out to 28 weeks. By then, patients lost up to 12.1% of their weight, when analyzing just those who stayed on treatment, as Pfizer previously reported. 

New data presented at the annual meeting of the American Diabetes Association on Saturday show that when patients transitioned from weekly to monthly dosing, the rate of weight loss continued at a similar pace; they had not yet hit a plateau by 28 weeks. That’s a promising sign, but the rate of weight loss at 28 weeks was still less than what was seen at a similar time point in the pivotal trial of Eli Lilly’s Zepbound.

Continue to STAT+ to read the full story…

Posted on

STAT+: Newer GLP-1s, pushback on research cuts, and a protest 

You’re reading the web edition of STAT’s ADA in 30 Seconds newsletter from the American Diabetes Association’s annual conference. Sign up here

This is Elizabeth Cooney saying hello from New Orleans, where the weather is warm, the conference center is cool, and debates can be fiery. Welcome to the first of three ADA in 30 newsletters, in which my colleague Elaine Chen and I curate some of the news and analyses circulating here near the banks of the mighty Mississippi.

First up, thoughts from Rick Woychik, a senior adviser to NIH chief Jay Bhattacharya who subbed for him as keynote speaker, plus some background from our STAT colleague Anil Oza. Then, what the weekend will bring.

If you are here too, come say Hi, or reach me at elizabeth.cooney@statnews.com.

Continue to STAT+ to read the full story…

Posted on

Evaluating an Abbreviated Internet-Delivered Stress Recovery Intervention for Health Care Workers: Pre-Post Feasibility Study of Outcomes, Usability, and Acceptability

<strong>Background:</strong> Health care workers face numerous occupational stressors that place them at heightened risk for burnout and poor mental health. Internet-delivered interventions have shown promise in reducing stress and related symptoms, yet adherence is often low, and users do not complete programs. Abbreviated interventions may help address engagement barriers such as high workload, limited time, and varying user preferences. There is a need to evaluate brief, accessible formats of internet-delivered programs for this population. <strong>Objective:</strong> This study aimed to examine the initial outcomes, usability, and acceptability of a 4-week abbreviated internet-delivered stress recovery intervention for health care workers. Specifically, it evaluated changes in stress recovery, perceived stress, depression and anxiety symptoms, and psychological well-being. The study also sought to understand participants’ experiences with the brief format to determine whether it meets their needs. <strong>Methods:</strong> This single-arm pre-post study examined a 4-week abbreviated version of the online guided cognitive behavioral therapy-based stress recovery program FOREST among self-enrolled health care workers recruited through professional networks (N=52; mean age 39.31, SD 11.31 years; 49/52, 94.2% women). Outcomes included stress recovery (the Recovery Experience Questionnaire), perceived stress (the Perceived Stress Scale-4), depression and anxiety symptoms (the Patient Health Questionnaire-4), psychological well-being (the World Health Organization Well-being Index), and usability and acceptability ratings. <strong>Results:</strong> We found that after the abbreviated version of the FOREST intervention participants showed moderate improvements in stress recovery (<i>d</i>=0.54, 95% CI 0.25-0.83); reductions in stress (<i>d</i>=–0.43, 95% CI –0.72 to –0.14), anxiety and depression symptoms (<i>d</i>=–0.51, 95% CI –0.80 to –0.22); and increase in psychological well-being (<i>d</i>=0.39, 95% CI 0.08-0.70). The majority (37/52, 71.2%) accessed all 6 modules. Users reported high satisfaction with the abbreviated program. <strong>Conclusions:</strong> While preliminary and limited by the pre-post design, these findings indicate that abbreviated internet-based stress recovery programs are a promising and practical tool for supporting the mental health of health care workers. Future research should examine the long-term effects, compare the abbreviated and standard versions, and explore implementation in routine practice. <strong>Trial Registration:</strong>
Posted on

Senior NIH official pushes MAHA strategy to skeptical ADA audience

NEW ORLEANS — A senior adviser to the leader of the National Institutes of Health opened his speech to a national gathering of diabetes researchers with a full-throated endorsement of the Make America Healthy Again movement. Then, during the fireside chat that followed, he withstood sustained cheers for criticism of deep funding cuts to the nation’s biomedical research enterprise that he was asked to explain.

“I could have written the MAHA agenda,” Richard Woychik, who works closely with NIH Director Jay Bhattacharya, said Friday, recalling when he first learned last October of the policy embraced by Health and Human Services Secretary Robert F. Kennedy Jr. 

Read the rest…

Posted on

How Germinal Centers Generate Antibodies Through Noisy Rounds of Mutation and Selection

A study tracking thousands of B cells across more than 100 germinal centers (GCs) in mice has revealed how the system consistently produces highly effective antibodies. The findings overturn longstanding ideas about how germinal centers function, revealing that they are far more selective than once thought, and challenge the idea that antibody improvement is driven mainly by rare growth “bursts” among the most successful B cells. The discovery could have implications for immune cell evolution, and ultimately guide the design of vaccines against rapidly mutating pathogens like influenza. It could also lead to new ways of studying evolution itself.

“The traditional, mechanistic view of germinal centers is to think of them as selection machines sorting out the best antibodies,” said research lead Gabriel D. Victora, PhD, head of the Laboratory of Lymphocyte Dynamics at The Rockefeller University. “But when you look very, very closely, you see a process that’s almost essentially random—a little bit better than a coin toss—which repeats many times until the immune system arrives at the right answer consistently. That’s much more akin to how evolution operates than the way a machine does.”

Victora and colleagues reported on their findings in Cell, in a paper titled “Replaying germinal center evolution on a quantified affinity landscape.”

Inside germinal centers, B cells rapidly mutate and compete to produce antibodies that bind successively better to pathogens. “Darwinian evolution of immunoglobulin genes within germinal centers (GCs) underlies the progressive increase in antibody affinity following antigen exposure,” the authors wrote. That puts B cells under intense pressure to optimize a single trait: binding affinity, or how well an antibody recognizes its target.

But how they accomplish that feat has very much remained an open question, the team noted. “Whereas the cellular mechanics of how competition between B cells increases affinity are well established, the evolutionary dynamics of this process are less clear.” Because weak and strong B cells often coexist side by side in the germinal center, scientists have long wondered whether the immune system temporarily preserves weaker cells in case they later acquire useful mutations. The phenomenon of clonal bursts, in which the descendants of a single B cell rapidly take over an entire germinal center, are also poorly understood.

The authors explained that GC B cells evolve by rapidly mutating only two Ig genes, which are the heavy chain (Igh) and light chain (either Igk or Igl). Victora’s team engineered mice in which all competing B cells began with the same antibody sequences, allowing them to replay a single evolutionary process across more than 100 germinal centers at once. “… we established a system in which GCs are composed entirely of B cells carrying the same pre-rearranged Igh and Igk genes, ensuring identical starting specificity and affinity,” they explained. Victora added, “We simplified it to the bare bones, and asked how repeatable is the exact sequence of mutations that leads to stronger antibodies.”

Once each of the B cells was primed with the exact same unmutated antibody sequence, the team triggered germinal center formation through immunization. They then tracked the resulting sprint toward immune efficiency with multiphoton microscopy and laser-based photoactivation, and sequenced thousands of individual B cells across 119 germinal centers.

With this data, the team managed to construct a detailed family tree that mapped how different lineages of B cells had developed. They also built a mutational dictionary, using deep mutational scanning (DMS), a technique that links almost every possible amino-acid change to antibody performance. This advance allowed the team to determine how mutations affected binding strength and structural stability simply by reading a cell’s DNA sequence.

“DMS was the big technical advance here,” says first author Ashni Vora, PhD, a graduate fellow in the lab. “With it we could determine the affinities of thousands of cells just by looking at their sequence, without having to produce an antibody.”

The researchers compare the resulting picture to a casino game. Watching a single B cell evolve inside a germinal center looked almost random, with some cells rapidly expanding, others disappearing, and even promising mutations failing as if random chance ruled the day. Some germinal centers were overtaken by clonal bursts while others contained many competing lineages with no clear winner. The differences had little to do with affinity or merit. “We find that, even in this simplified setting, GC selection yields widely divergent tree topologies, ranging from clonal-burst-type structures to multi-pronged GCs where multiple line ages evolve in parallel,” they noted.

But the team discovered that the germinal center game is rigged. In a casino, the house always wins not because of the odds on any individual game, but because a slight statistical bias is built into the system and repeated thousands of times. Germinal centers appear to operate similarly. Each round of cellular competition is only slightly biased toward cells carrying beneficial mutations, and random chance means that there is often little correlation between affinity and success. But by repeating that same noisy, almost random process over and over across many germinal centers, the immune system ultimately produces stronger antibodies.

“If you see someone get a jackpot, you might wonder how the casino makes money,” Victora says. “The answer is that the casino puts in a little bit of bias, so that you win and you lose, but on average, you lose more than you win. If there are just one or two people playing, the casino might lose money due to random chance. But if there are a thousand people playing, it’s going to average out and the house wins. That’s essentially how germinal centers work.”

The researchers also found that the immune system favors mutations that are easiest for its cellular machinery to generate, rather than the mutations that would produce the strongest antibodies. And by tracking B cell lineages over time, they also showed that germinal centers are far more selective than previously thought, rapidly eliminating inferior B cells. “By combining phylogenetic reconstructions with a fitness landscape inferred from populations sampled over time, we show that both the apparent permissiveness of GCs to low-affinity lineages and the apparent early plateau in affinity maturation are best explained by survivorship biases that distort the histories of lineages present at sampling,” the investigators wrote in summary.

Taken together, the findings overturn several longstanding ideas about how germinal centers function and may provide new tools for vaccine developers hoping to steer antibody evolution against influenza and HIV. “What was once theoretical speculation about what must happen in the germinal center, we are now showing in action—the real thing,” Victora says.

At the same time, this work also illustrates how germinal centers could become a powerful model for studying evolution more broadly. Scientists have long relied on bacteria grown in the lab over many generations to plumb the depths of evolutionary biology and determine how much of evolution is driven by random chance. In clarifying the rules governing germinal centers, the researchers revealed why the immune system could offer a potentially more tractable experimental avenue: Unlike bacterial evolution, which centers around adapting to many possible survival strategies, B cells are all aiming for the same target. “I see this as an opening salvo in a longer effort to understand evolution by using the immune system as a model,” Victora added.

The post How Germinal Centers Generate Antibodies Through Noisy Rounds of Mutation and Selection appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Using Social Media to Maximize the Research Impact of Surgeons: Exploratory Linguistic Analysis

Background: Surgeons work in a progressive field where communicating research is vital to advancing health care and enabling meaningful interactions among clinicians. It also contributes to societal impact, increases access to information, and reduces misinformation. Additionally, there can be barriers to accessing papers. Social media enhances research impact through sharing scholarly work and improving its translation into clinical practice, but little is known about how to design specific posts to maximize research impact through language. Objective: The purpose of this study was to determine the linguistic cues that optimize research impact among surgeons through Twitter (subsequently rebranded X). Additionally, this research combines the linguistic features of the posts and article access to determine their unique contributions. Methods: An exploratory linguistic analysis of 84 posts extracted from Twitter was conducted, which shared scholarly activity by 17 of the most-followed surgeons. The linguistic cues were measured on a continuous scale, computed from the percentage of each linguistic cue used in the text, and reported as mean (SD). Regression analysis and analysis of covariance were conducted to determine which cues influenced research impact and to estimate the potential association with study accessibility (open vs restricted access). Results: Analyzed tweets were highly analytic (mean 94.77, SD 9.00), moderate in clout (mean 42.69, SD 19.84), low in tone (mean 20.06, SD 33.91), suggesting negative tone use, and low in authenticity (mean 19.52, SD 24.50). Results suggest that a high use of formal language negatively impacts readership and citations. Analytical language was indirectly associated with readership (β=−0.296, 95% CI −423.57 to −59.95; =.01) and citations (β=−0.524, 95% CI −0.442 to −0.187; <.001). Linguistic clout had a positive association with readership (β=0.260, 95% CI 8.58-186.91; =.03), and tone in tweets had a negative association with readership (β=−0.317, 95% CI −138.52 to −5.39; =.04). Negative language tone was found to increase the impact of research. With respect to linguistic cues and study accessibility, the results also suggest that the number of citations was impacted by readership (=4.11, 95% CI 2.459E-06 to 0.003; =.047) and analytic linguistic cues (=18.77, 95% CI −0.402 to −0.149; <.001) used in the post, but the association of open (mean 3.04, SE 1.062) versus restricted access (mean 1.83, SE 0.716) was not statistically significant (=0.877, 95% CI 0.405-3.266; =.352). Conclusions: This research is the first to explore article accessibility and linguistic cues used in creating posts that share research on social media to determine their influence on research impact, making this study both innovative and unique relative to existing studies in the surgery field. Through language, the medical field can expand its impact and encourage dialogue between scientists and the public, thereby increasing scientific and societal contributions while reducing the negative effects of limited article access.
Posted on

Blood-Based Risk Score Could Enable Earlier Lung Cancer Prevention

Researchers have identified a 14-protein blood signature capable of predicting lung cancer risk more than five years before diagnosis, potentially opening the door to a new era of precision cancer prevention.

The study, published in Cell by investigators at The Francis Crick Institute and University College London (UCL), combines large-scale human population data, mechanistic laboratory studies, and clinical trial analyses to demonstrate that a blood-based inflammatory signature can identify individuals at elevated risk of lung cancer and may pinpoint those most likely to benefit from preventive treatment.

The findings move beyond traditional risk models based on age and smoking history and offer what researchers describe as a potential equivalent of cholesterol testing for lung cancer prevention.

Moving beyond smoking-based risk assessment

Current lung cancer screening programs primarily target older individuals with a history of smoking. While smoking remains the leading risk factor, many lung cancers arise in people who would not qualify for screening under existing criteria, including never-smokers and individuals exposed to environmental pollutants.

The research team sought to develop a biologically informed method of identifying risk by focusing on inflammation, which has emerged as a critical driver of tumor development.

Previous work from the group demonstrated that air pollution can promote lung cancer by triggering inflammatory responses that awaken dormant cells carrying cancer-causing mutations. The new study aimed to determine whether this inflammatory state could be detected in the blood before cancer becomes clinically apparent.

Machine learning identifies a 14-protein signature

Using plasma protein measurements from more than 48,000 participants in the UK Biobank, researchers applied machine learning approaches to identify blood proteins associated with future lung cancer diagnoses.

The algorithm incorporated conventional risk factors such as age, smoking status, prior lung disease, and plasma protein profiles. Analysis revealed a panel of 14 circulating proteins that consistently predicted lung cancer risk within five years of diagnosis.

The signature was validated across eight independent international datasets and remained predictive across diverse populations, including a cohort composed entirely of non-smokers.

Individuals who later developed lung cancer consistently exhibited elevated levels of the signature years before their diagnosis.

“This is a proof of concept that, one day, we could use this signature to offer preventive treatment to people at risk of lung cancer,” said Tej Pandya, clinical PhD student at UCL and visiting scientist at The Francis Crick Institute.

Detecting an inflammatory state before cancer emerges

One of the study’s most significant findings is that the signature appears to reflect a pre-cancerous inflammatory environment rather than the presence of an undetected tumor.

The researchers found evidence that the protein profile originates from changes within the lung microenvironment before malignant transformation occurs.

Further analyses showed that the same signature was elevated in individuals who later developed chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis, suggesting it may identify a broader inflammatory state that predisposes individuals to multiple lung diseases.

Studies in mouse models provided additional support for this hypothesis. Exposure to air pollution increased both the protein signature and the abundance of a cellular state known as KAC cells—adaptive cells that emerge during tissue injury but can become malignant when cancer-driving mutations are present.

Mutant cells arising from several distinct lung cell populations converged on this same KAC state during the earliest stages of cancer development.

Linking air pollution, inflammation, and cancer

The findings build on earlier research implicating the inflammatory cytokine interleukin-1 beta (IL-1β) as a critical mediator of pollution-driven lung cancer.

The investigators demonstrated that air pollution exposure increased IL-1β signaling, elevated components of the 14-protein signature, and expanded KAC cell populations.

Blocking IL-1β in mice reduced KAC cell numbers and slowed early tumor formation, providing experimental evidence that inflammatory signaling contributes directly to cancer initiation.

These observations suggest that the blood signature may serve not only as a risk marker but also as a biological indicator of an underlying process that can be therapeutically targeted.

Revisiting a major clinical trial

To determine whether the signature could identify patients most likely to benefit from preventive intervention, the researchers revisited data from the landmark CANTOS trial.

The trial originally evaluated the IL-1β inhibitor canakinumab for cardiovascular disease prevention and unexpectedly reported reduced lung cancer incidence as an exploratory outcome. However, the overall cancer-prevention benefit appeared too modest to justify widespread use of the drug for this purpose.

The new analysis tells a different story.

Researchers examined data from 4,651 CANTOS participants and found that individuals with elevated levels of the 14-protein signature experienced the greatest benefit from canakinumab treatment. In this high-risk subgroup, lung cancer incidence was nearly cut in half.

By restricting treatment to those identified by the biomarker signature, the number needed to treat to prevent one lung cancer case fell to 55, a figure comparable to widely accepted cardiovascular prevention strategies such as statin therapy.

Toward precision cancer prevention

The work represents a shift in how researchers think about cancer prevention.

Rather than treating large populations indiscriminately, the study suggests that molecular biomarkers could identify individuals in a reversible pre-disease state and guide targeted interventions before cancer develops.

“Drugs like statins have transformed the prevention of cardiovascular disease, used to treat individuals with a high low-density lipoprotein (LDL),” said Charlie Swanton, FRCP, PhD, clinical research director at The Francis Crick Institute and professor of cancer at UCL.

“But we don’t yet have an LDL-like marker of risk or a statin for lung cancer.”

Swanton added that identifying an inflammatory state before tumor formation provides a potential “window of opportunity” in which preventive treatment could be most effective.

Implications beyond lung cancer

The investigators note that the inflammatory signature may reflect a broader biological phenomenon associated with aging and chronic disease.

Because the signature was also associated with future COPD and pulmonary fibrosis, it may represent a shared pre-symptomatic inflammatory state that precedes multiple age-related lung disorders.

If validated in prospective studies, the approach could ultimately support routine blood-based risk assessment and targeted prevention strategies not only for lung cancer but potentially for other inflammation-driven diseases.

For now, the findings provide one of the strongest demonstrations yet that cancer risk can be detected years before diagnosis and that those biological signals may be actionable.

The challenge ahead will be determining whether identifying high-risk individuals and intervening early can translate into measurable reductions in lung cancer incidence, a question future prospective prevention trials will seek to answer.

The post Blood-Based Risk Score Could Enable Earlier Lung Cancer Prevention appeared first on Inside Precision Medicine.