BackgroundThe relationship between adverse childhood experiences (ACEs) and personality disorders (PDs) has attracted sustained attention in psychiatry, psychology, and public health. Existing studies have mainly examined epidemiological associations, specific PDs diagnoses, or mechanisms, whereas bibliometric evidence mapping the field’s knowledge structure and thematic evolution remains limited. This study aimed to characterize trends, contributors, collaboration networks, core themes, and frontiers in ACEs–PDs research.MethodsEnglish-language publications on ACEs and PDs were retrieved from Web of Science Core Collection, Scopus, and PubMed from inception to December 31, 2025. After year screening, document-type filtering, and deduplication, 5,084 records were included. Bibliometric analyses were performed using R, VOSviewer, and CiteSpace. The merged dataset was used to examine annual trends, countries/regions, institutions, authors, journals, and keyword co-occurrence, while WoSCC records were used for co-citation analysis, keyword clustering, and burst detection.ResultsACEs–PDs research showed sustained growth, with a marked increase after 2000. The United States occupied a central position in publication output, citation impact, and international collaboration, while the United Kingdom, Germany, Canada, the Netherlands, and Australia also showed strong influence. Harvard University, the University of London, and Ruprecht Karls University Heidelberg were leading institutions; Zanarini M, Fonagy P, Schmahl C, Paris J, and Kleindienst N were key contributors. Influential journals mainly covered psychiatry, personality disorders, child maltreatment, trauma, and developmental psychopathology. Keyword analyses identified childhood adversity, personality disorder, borderline personality disorder, depression, childhood sexual abuse, and post-traumatic stress disorder as core themes. VOSviewer and CiteSpace analyses indicated that hotspots have expanded from childhood abuse, PDs diagnosis, and psychiatric comorbidity to emotion dysregulation, non-suicidal self-injury, social support, functional connectivity, early intervention, and mechanism validation. Highly cited publications revealed a knowledge base centered on childhood abuse/trauma, borderline personality disorder, psychiatric comorbidity, emotion regulation, and neurobiological mechanisms.ConclusionThis study maps development and knowledge structure of ACEs–PDs research. Findings suggest a shift from exposure–outcome association studies toward comorbidity, intermediate phenotypes, neurobiological mechanisms, and clinical translation. Future research should strengthen longitudinal and cross-cultural designs, consider ACE type, timing, duration, and severity, and integrate neuroimaging, inflammatory, epigenetic, and clinical-course phenotypes.
Prevalence of depression in patients with advanced cancer receiving palliative care: a meta-analysis of self‐report instruments
BackgroundAlthough the prevalence of depression in patients with advanced cancer receiving palliative care has been widely reported, the estimates vary substantially. This meta-analysis aimed to determine the pooled prevalence of depression in patients with advanced cancer receiving palliative care and identify its potential moderating factors.MethodsA comprehensive literature search was conducted in PubMed, Web of Science, Scopus, Embase, Cochrane Library, CINAHL, and PsycINFO from inception to April 1, 2026. We calculated pooled prevalence estimates using a random-effects model and assessed heterogeneity using the I² statistic. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity.ResultsA total of 29 studies comprising 6054 patients with advanced cancer receiving palliative care were included, yielding a pooled prevalence of depression of 50.9% (95% CI: 41.2-60.5%). Subgroup analyses and meta-regression showed that the pooled prevalence varied significantly by study design and assessment tool.ConclusionsOur findings indicated that depression was very prevalent in patients with advanced cancer receiving palliative care. However, the pooled estimate should be interpreted with caution because the extremely high statistical heterogeneity remained largely unexplained, even after conducting subgroup analyses and meta-regression. Furthermore, the adoption of suitable assessment tools and the implementation of valid screening and care strategies are essential to alleviate emotional distress in this vulnerable group.Systematic review registrationPROSPERO, identifier CRD420261368352
<![CDATA[Phase 2 IRIS finds ML-004 misses social communication goals in autism, but notably reduces irritability in teens.]]>
Three Subtypes of Severe Pneumonia Might Inform Personalized Therapies
The results of a study headed by researchers at the University of Cambridge suggest that severe pneumonia has three different subtypes, a discovery that could help to explain why some patients in intensive care units (ICUs) recover from their illness faster than others, and for some patients, the disease can be life-threatening. Rather than assessing patients’ symptoms, the Cambridge team analyzed fluid taken from the lungs of patients admitted to the hospital with suspected pneumonia. Their results indicated that although each of the three different “pneumotypes” of severe pneumonia was associated with how the patients recovered, none could be reliably identified using standard blood tests.
The researchers suggest that their findings could in the future help inform personalized therapeutic strategies, allowing individual patients to receive the most appropriate treatment. Andrew Conway Morris, PhD, at the Department of Medicine at the University of Cambridge and an ICU consultant at Addenbrooke’s Hospital, Cambridge, is senior author of the team’s published paper in Nature Communications, titled “Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes.”
Pneumonia is the commonest infectious cause of death worldwide, responsible for an estimated 2.5 million deaths per year, the researchers noted. In severe cases, patients may need to be admitted to an ICU and given mechanical ventilation. Severe pneumonia accounts for six in 10 infections managed in intensive care, and spread of the infection within ICUs is a significant concern.
Doctors have long struggled to understand why patients whose condition looks similar clinically can have very different recoveries. Some respond quickly to treatment, while others remain critically ill for weeks or even die. “Despite the considerable burden of pneumonia, the syndrome is incompletely understood, and diagnosis is difficult,” the team explained.
Conway Morris said, “Even though we’re able to treat the initial infection, many patients with severe pneumonia still struggle to come off the ventilator and can develop lung failure. Therapies to tackle inflammation in the lungs have had mixed results in clinical trials—some suggest they are beneficial, others that they’re harmful.”
Severe pneumonia is usually diagnosed through a combination of symptoms, imaging, and blood tests. Symptoms typically include fever or hypothermia, low oxygen levels, breathing difficulties, and confusion. “The current approach of classifying patients by their clinical syndromes—sepsis, acute respiratory distress syndrome, and so on—without looking at the underlying biology risks missing what’s key,” Conway Morris noted. “Instead of asking ‘Does this patient have pneumonia?’, we should be asking ‘What’s the inflammatory pattern in this patient’s lungs?’”
For their newly reported study, Conway Morris and team recruited 80 patients admitted with suspected severe pneumonia to the ICU at Addenbrooke’s Hospital. Instead of relying only on blood tests or scans, however, the Cambridge team analyzed the patient’s immune cells, inflammatory signals, and gene activity in bronchoalveolar lavage samples. “Here, we perform multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically characterise a cohort of patients with suspected severe pneumonia,” they reported in their paper. The researchers discovered three distinct biological types—or pneumotypes (Pn)—of severe pneumonia, none of which could be reliably detected using standard blood tests, even though they were strongly linked to how patients recovered.
“Using bulk RNA sequencing of bronchoalveolar fluid, we have identified three phenotypes in the lungs of patients with lung injury and suspected pneumonia,” they stated. “These phenotypes were reflected in the differential immune cell populations and inflammatory proteins.”
The most common pneumotype—accounting for almost half (49%) of cases—was characterized by immune suppression, significant damage to the lining of the lungs, and bleeding in the alveoli (tiny air sacs within the lungs). There were fewer signs of inflammation, which may explain why treatments targeting inflammation can fail or even harm some patients. “Pn1, the most common, is characterized by low alveolar cytokines, expanded tolerogenic macrophages, and epithelial damage,” the investigators reported.
The second pneumotype—accounting for just under a quarter (23%) of cases—was characterized by a balanced immune response and active repair of damage to the lungs. Patients were most likely to recover faster from this pneumotype and require the shortest time on the ventilator, even though they initially looked just as ill as the others. “Pn2 displays the fastest resolution, exhibiting a balanced immune response and epithelial-endothelial repair signatures,” they continued.
Patients with the most dangerous pneumotype—the one that most resembles “classic” pneumonia—spent the longest on mechanical ventilation and had prolonged critical illness. They had severe and persistent inflammation, with a flood of immature immune cells in the lung. This group may be most likely to respond to anti-inflammatory therapies, the team said. “Pn3 is characterized by immature neutrophil infiltration, IL-6-STAT3 activation, and longer duration of mechanical ventilation,” the scientists stated.
First author Dr. Mark Jeffrey, at the Department of Medicine at the University of Cambridge, added, “Even though on the surface, all of the patients seemed to have similar types of pneumonia, with comparable illness severity, oxygen levels, and clinical diagnoses, their outcomes were very different. It was only when we drilled down and looked at patterns of inflammation that the differences became apparent. Severe pneumonia is not a single disease, but several biologically distinct conditions that happen to look alike. This helps explain why ‘one-size-fits-all’ treatments—including some immune-modulating drugs—have often failed in clinical trials.”
Interestingly, the authors added in their report, “Each of the Pneumotypes contained both patients with and without confirmed pneumonia, implying common mechanisms underpinning lung injury arising from different mechanisms.”
The tests used to determine the pneumotypes are too complex to enable rapid classification, but the researchers hope to develop a simplified tool that could help them stratify the patients and ultimately offer tailored treatments.
Co-author Vilas Navapurkar, MBChB, from the John Farman Intensive Care Unit at Addenbrooke’s Hospital, said, “If we know which subtype of pneumonia an individual has, we can potentially tailor their treatment more precisely, boosting the immune response in some, while calming harmful inflammation in others. This has the potential to help critically ill patients, reduce deaths from pneumonia, shorten ICU stays, and cut unnecessary antibiotic use.”
The team also noted that while their study identified three Pneumotypes, it’s likely that others may exist, which might be identified in larger studies. In conclusion, they wrote, “… we have identified and validated three pulmonary confined endotypes in patients with severe pneumonia and lung injury. These phenotypes are underpinned by distinct mechanisms and have differential outcomes. The mechanisms point to different therapeutic options, as well as extending our understanding of the biology of lung inflammation in the context of severe pneumonia.”
The post Three Subtypes of Severe Pneumonia Might Inform Personalized Therapies appeared first on GEN – Genetic Engineering and Biotechnology News.
Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome
A University of California, Riverside-led research team has developed a gene therapy that restored production of a missing brain protein, corrected abnormalities in brain circuitry, and improved behavior in a mouse model of Fragile X syndrome (FXS). The study, published in the journal Molecular Therapy Nucleic Acids, tested an adeno-associated virus (AAV)-based therapy carrying a normal human version of the FMR1 gene to produce the Fragile X messenger ribonucleoprotein (FMRP) and found that early treatment normalized several measures of brain activity while improving social behavior, exploratory behavior, and cognitive flexibility.
“In a typical brain, FMRP acts like a brake or a volume control,” said senior author Iryna Ethell, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine. “Without it, neural circuits become overactive and less efficient, which contributes to many of the developmental and behavioral challenges associated with FXS.”
FXS is the most common single-gene cause of autism spectrum disorder. According to the researchers, the disorder typically manifests from expansion of CGG repeats in the 5′ untranslated region of FMR1. The mutation causes methylation and silencing of the gene, leading to a major reduction or complete loss of FMRP, an RNA-binding protein that regulates numerous messenger RNAs involved in synapse formation, maturation, and function. Loss of the protein can lead to abnormal synaptic activity and increased cortical hyperexcitability.
FXS can produce sensory hypersensitivity, seizures, anxiety, intellectual disability, developmental delays, repetitive behaviors, and social communication difficulty. Current treatments for this syndrome don’t seek to cure it, rather they are aimed at managing the associated symptoms of anxiety, hyperactivity, irritability, aggression, depression, and seizures.
The therapy developed by the research team was designed to replace missing FMRP rather than repair the original mutation. To do this, the researchers used an AAV9 viral vector to deliver human FMR1 isoform 7, one of the most abundant forms of the protein found in the brain. The therapy was tested in newborn mice lacking FMRP via intracerebroventricular injections at either a low or high doses.
The work built on earlier research that explored the potential of AAV-mediated restoration of FMRP in rodent models. These prior studies used a range of viral serotypes, promoters, delivery routes, and FMRP isoforms and showed they could partially or completely correct specific biochemical, physiological, and behavioral abnormalities. The researchers noted that studies involving mouse and rat FMRP homologs had shown that restoring the protein could improve a range of Fragile X-related deficits.
The current study showed that high-dose treatment produced the strongest positive effects in the mouse models. Electroencephalography showed normalization of baseline gamma power, improvements in responses to sound, reduced background neural activity, and improved habituation to repeated auditory stimuli. The therapy also restored abnormal patterns of brain-wave coupling that have been associated with Fragile X-related dysfunction.
Behavioral testing showed that these improvements persisted into adulthood. Mice receiving the higher dose displayed normalized exploratory behavior, improved social preference, and better performance in probabilistic reversal learning, a measure of cognitive flexibility that requires adapting when previously rewarded behaviors stop producing rewards.
“Fragile X mice tend to persist with an old solution even after the rules change,” Ethell said. “After treatment, they became much better at adapting, performing similarly to mice with normal FMR1 function.”
The researchers noted that their work showed the importance of delivering at therapy for FXS early in its development. They said that widespread distribution of the potential new gene therapy throughout the brain was necessary to achieve a therapeutic benefit. There was a clear relationship between the proportion of neurons expressing the therapeutic gene and the degree of functional recovery, which indicated that restoring FMRP in a sufficient number of cortical cells is critical for correcting any behavioral deficits.
While a promising step, the investigators said that the work was a preclinical study and that future research will now focus on developing delivery methods that can of have broad distribution across the human brain. The team also believes their approach could have broader applications.
“Beyond FXS, the findings may provide a roadmap for treating other genetic neurodevelopmental disorders caused by the loss of a single critical protein,” Ethell said. “Our study shows it may be possible to restore function across complex brain networks by replacing a missing gene. That gives us reason to be optimistic about the future of genetic medicine.”
The post Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome appeared first on Inside Precision Medicine.
Cognitive-attitudinal factors predict CBT-I enrollment willingness in Chinese sleep clinic patients: a knowledge-attitudes-practices survey
BackgroundDespite strong evidence for cognitive behavioral therapy for insomnia (CBT-I), uptake remains constrained by poorly understood cognitive, attitudinal, and practical barriers. This study examined determinants of willingness to enroll in sleep improvement programs among adults at risk of sleep disorders—including insomnia, obstructive sleep apnea, and comorbid psychological distress—attending a tertiary sleep clinic in China.MethodsA cross-sectional knowledge-attitudes-practices survey was conducted among 2,661 adults attending the sleep and behavioral medicine outpatient clinic at Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi, China, between February 2022 and June 2025. Willingness to enroll in a structured sleep improvement program was assessed alongside sleep health knowledge, perceived need, CBT-I versus medication effectiveness beliefs, telehealth acceptability, clinical severity (Insomnia Severity Index, Epworth Sleepiness Scale, STOP-Bang), psychological symptoms (PHQ-2, GAD-2), perceived barriers, and sociodemographic characteristics. Multivariable logistic regression identified independent predictors of willingness to enrollment, with secondary analyses evaluating model discrimination and testing prespecified interactions.ResultsAmong 2,661 participants (median age 45 years, 56.5% female, median ISI = 13), 1,386 (52.1%) expressed willingness to enroll. Univariable comparisons showed no significant differences between willing and not-willing groups across demographics, clinical characteristics, or barriers (all p>0.05). However, multivariable modeling revealed that when considered simultaneously, cognitive-attitudinal factors emerged as significant independent predictors, suggesting complex interactions rather than simple bivariate associations. In multivariable models, perceived need (OR = 1.20, 95% CI: 1.16–1.25, p<0.001), beliefs that CBT-I is more effective and durable than sleep medication (OR = 1.12, 95% CI: 1.08–1.16, p<0.001), sleep health and treatment knowledge (assessed by a six-item knowledge score) (OR = 1.09, 95% CI: 1.05–1.13, p<0.001), and anxiety symptoms (OR = 1.07, p=0.005) positively predicted willingness. Paradoxically, depression symptoms (OR = 0.94, p<0.001) and insomnia severity (OR = 0.93, p<0.001) inversely predicted willingness. Model discrimination was modest (AUC = 0.543, 95% CI: 0.504–0.590). Time (mean 3.54) and cost (3.44) were most severe barriers but showed no independent association with willingness (p>0.05).ConclusionCognitive-attitudinal factors (perceived need, CBT-I beliefs, knowledge) independently predicted enrollment willingness, whereas demographics and practical barriers did not. Depression and insomnia severity paradoxically reduced willingness, creating an inverse care law. However, poor model discrimination and measurement of stated willingness rather than actual enrollment limit conclusions. Prospective validation and motivational enhancement strategies for patients with depression are needed.
STAT+: Another big deal, another sign biotech M&A is back
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Good morning! Pharma companies are on a biotech buying spree, an LSD pill just delivered unusually strong late-stage depression data, and the FDA reverses course of Regenxbio’s treatment.
Also: Today, thousands of industry players (and me!) are gathering in San Diego for BIO to talk deals, science, and whatever comes next. Check out the last item for a jaunt down memory lane about the conference.
StockWatch: Positive Phase III Data Sells Investors on Intellia
A second positive Phase III data readout in two months is a major reason why Intellia Therapeutics (Nasdaq: NTLA) shares have soared more than 76% over the past six months—including a 29% surge this past week that followed the CRISPR gene editing therapy developer’s lead pipeline candidate lonvoguran ziclumeran (lonvo-z) meeting three key secondary endpoints in a pivotal study in patients with hereditary angioedema (HAE).
Lonvo-z met the Phase III HAELO trial’s (NCT06634420) primary endpoint, Intellia announced back in April, by showing an 87% reduction (p<0.0001) in mean monthly attacks in the lonvo-z arm vs. the placebo arm during the efficacy evaluation period (weeks 5-28). Lonvo-z also aced the trial’s key secondary endpoint by showing that 62% of the 52 patients in the lonvo-z arm were entirely attack-free and therapy-free for the six-month efficacy evaluation period, vs. just 11% of the 28 patients in the placebo arm (p<0.0001).
On June 13, Intellia presented and published additional data showing lonvo-z to have achieved positive results on three other key secondary endpoints:
- Monthly rate of attacks requiring on-demand treatment, Weeks 5–28, mean (0.19 vs. 1.79, 95% CI).
- Monthly rate of moderate/severe attacks, Weeks 5–28, mean (0.11 vs. 1.23, 95% CI).
- Change from baseline to Week 28 in AE-QoL total score, mean ( — 23.51 vs. — 6.47, 95% CI).
Intellia presented the data at the European Academy of Allergy & Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul, Türkiye, and published the results in The New England Journal of Medicine.
The data was strong enough for Intellia to continue the rolling Biologics License Application (BLA) submission that it began in April. The company expects to complete the BLA filing by year’s end and hopes to gain FDA approval and launch lonvo-z in the first half of 2027.
“Super pleased”
“We were super pleased with the results that we saw,” John Leonard, MD, Intellia’s president and CEO, told GEN. “We’re essentially replicating what we’ve seen throughout the program, where most of the patients reached a status of no attacks, no therapies over the course of this extended observation period. For those patients who didn’t, they appeared to be on their way to reaching that kind of a state. And critically important was that every single patient who got the drug was off long-term prophylaxis.”
“Across the board, and across all subgroups, the drug performed extremely well. So, we think it speaks to physicians, it’s going to speak to payers in terms of how they think about the drug and its ultimate, excellent utility,” Leonard said.
Investors and analysts appeared to share that enthusiasm this past week, as Intellia’s stock price rose over three of the four trading sessions following the release of data on the secondary endpoints. Intellia shares jumped 23% on June 15, the first trading day since the news, rising from $12.11 to $14.92. After a day of profit-taking that saw shares dip 2.5%, to $14.55, Intellia’s stock resumed its upward trajectory, rising nearly 4.5% to $15.20 on Wednesday, then another 3% Thursday, closing the week at $15.67. Markets were closed on Friday for the Juneteenth holiday.
Since December 18, 2025, when Intellia shares closed at $8.88, the stock has soared nearly 76.5%, accounting for most of its one-year gain of 62%. Lonvo-z accounted for three of Intellia’s four stock price peaks in 2026: The dosing of the first patient in HAELO, announced January 22, led the stock to climb 13%, from $14.03 to $15.90.
Shares surged 12% March 2, from $13.78 to $15.44, when the FDA lifted a clinical hold on the company’s Phase III MAGNITUDE trial (NCT06128629) assessing nexiguran ziclumeran (nex-z) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The FDA imposed the hold after an elderly patient died during a study of Nex-z, an in vivo CRISPR-based therapy developed in partnership with Regeneron Pharmaceuticals (Nasdaq: REGN) to treat ATTR-CM by inactivating the TTR gene.
The third peak, an 8% gain from $15.31 to $16.57 on April 22, followed Intellia reporting positive data for lonvo-z, showing that it met HAELO’s primary endpoint, while the fourth peak followed the secondary endpoint announcement.
Misperceived market
“Hereditary angioedema has, in the last 10 to 15 years, had a variety of therapies arrive that are better than the ones that were there 20 years ago. Twenty years ago, circumstances were pretty grim for patients with HAE,” Leonard recalled. “I think some investors have looked at this incorrectly as a satisfied market, only because there are other therapies available.”
Among those therapies are three that won FDA approval last year. Last August, the agency approved Dawnzera® (donidalorsen), a prekallikrein-directed antisense oligonucleotide designed to prevent HAE attacks in patients ages 12+, marketed by Ionis Pharmaceuticals (Nasdaq: IONS). A month earlier, the FDA authorized Ekterly® (sebetralstat), a plasma kallikrein inhibitor indicated for the treatment of acute attacks of HAE in patients ages 12+, marketed in the United States by KalVista Pharmaceuticals (Nasdaq: KALV).
And in June 2025, the FDA approved Andembry® (garadacimab-gxii), an activated Factor XII (FXIIa) inhibitor (monoclonal antibody) and the first long-term prophylactic HAE treatment designed to target Factor XIIa, administered as a once-monthly subcutaneous injection for patients ages 12+, marketed by CSL Behring, the largest business unit of Australian-owned CSL (ASX: CSL).
“What we’re showing is that a lot of efficacy and a lot of utility has been left on the table, and that it’s possible for patients to get pretty close to something resembling a normal person who does not have HAE and all of the things, benefits that come with that,” Leonard said. “As people have looked at the data more completely, I think they’re seeing more and more that that’s the case, and maybe some of those original premises that they had are not quite correct.”
In research notes, three analysts said Intellia’s latest data strengthened the company’s future case to regulators for pursuing approval of lonvo-z as a one-time HAE treatment.
“We view these data as furthering Intellia’s case for regulatory approval following its expected completion of a rolling BLA,” Myles R. Minter, PhD, a partner and biotechnology analyst with William Blair, wrote June 15.
A day earlier, Jefferies equity analyst Maury Raycroft, PhD, commented that Intellia’s latest data will help lonvo-z gain more than a foothold in the HAE market.
“Positive implications”
“Big picture, we believe total HAE data have positive implications for commercial positioning” of lonvo-z, Raycroft wrote. “Editing is expected to be durable (we have seen longer term ph.I/II data out to 3-yrs); therefore, NTLA’s approach could eliminate need for lifelong chronic tx [therapy], justifying the value proposition of a 1X tx, despite competition in a crowded HAE space.”
Raycroft cited market research from Intellia showing that 64% of surveyed patients on LTPs [long-term prophylaxis drugs] are extremely likely to transition to a one-time therapy, while 54% surveyed docs expressed intent to prescribe such a treatment.
Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink Partners, said Intellia’s latest results “again demonstrate lonvo-z’s clean safety and best-in-class efficacy and convenience.”
Writing in NEJM, the team of HAELO investigators reported no serious adverse events in patients treated with lonvo-z: “The most common adverse reactions were infusion-related reactions, which were generally transient and resolved without intervention. Elevated levels of serum aspartate aminotransferase and alanine aminotransferase, which occurred in approximately 10 to 15% of patients treated with lonvo-z, were transient, asymptomatic, and resolved without intervention.”
Foroohar sided with optimistic investors over their pessimistic counterparts in arguing that patients will warm up to a one-time treatment, though it will likely be costlier than current therapies.
Bears and bulls
“Bears argue limited patient demand to move up the innovation curve in a market with several approved treatments. We take the other side of this and see onetime therapy (vs lifetime chronic dosing) and patient desire to be attack-free as potent tailwinds to adoption,” Foroohar wrote. “Longer follow-up and crossover data (caveat – small n [number of patients studied]) provide an early glimpse at the improving profile of lonvo-z over time. We look to more data ahead of 1H27 launch to further educate physicians/patients.
“Subgroup analyses demonstrate clear benefit across all patient populations (prior LTP use, historical attack severity/frequency, etc.), supporting broad uptake as SoC [standard of care] across HAE—recognizing this will take time to play out as physicians gain comfort with this (likely) first approved in vivo gene editing therapy,” Foroohar added.
Intellia has not set a price for lonvo-z.
“We have said publicly we’re not going to set any new records beyond prices that have been precedented,” Leonard said.
HAE patients, he continued, “are some of the most costly patients that payers have. They’re small in number, but high in cost, with the therapies they take and their healthcare resource utilization exceeding $1 million a year.
“When you consider that these are patients that are oftentimes treated, or first diagnosed in adolescence or young adulthood, the lifetime costs are frighteningly high,” Leonard explained. “We are confident that, and we have this as an intended outcome, that we will save lifetime health, resources in very, very substantial terms, in a way that payers see and can recognize. We want to make it easy for patients to get onto the therapy, and we want to make it very competitive, cost-competitive for physicians taking care of them.”
Leaders and laggards
- Elicio Therapeutics (Nasdaq: ELTX) shares plunged 72.5% from $14.85 to $4.08 on June 15 after the developer of immunotherapies to treat high-prevalence cancers said it was evaluating multiple strategic financing and partnership opportunities to advance its planned Phase III adjuvant pancreatic cancer immunotherapies program and broader AMP platform. The action came after ELI-002 7P, a 7-peptide formulation of its lead candidate ELI-002, failed the Phase II AMPLIFY-7P trial (NCT05726864) in patients with mKRAS-driven pancreatic ductal adenocarcinoma (PDAC). ELI-002 7P missed the pre-specified primary endpoint of disease-free survival (DFS) in the intent-to-treat population. Elicio said the ELI-002 7P arm had a higher proportion of R1 resected (higher residual disease) patients vs. the observation arm (19% vs. 10%), and that post-hoc analyses showed significant DFS improvement (R0: HR 0.65, p=0.048) in the 121 lower residual disease (R0 completely resected) patients, a subgroup representing approximately 84% of enrolled patients. Elicio said the trial results will shape a Phase III strategy focused on a defined R0 resected population and additional ELI-002 7P dosing.
- Neumora Therapeutics (Nasdaq: NMRA) shares plummeted 49% from $1.78 to 91 cents on June 15 after the brain disease drug developer said it was chopping its workforce by approximately 35% or about 34 jobs, ending development of its major depressive disorder (MDD) candidate navacaprant, and refocusing on advancing the rest of its pipeline. The actions came after navacaprant missed statistical significance on the primary and key secondary endpoints of the Phase III KOASTAL-2 trial (NCT06058013) and KOASTAL-3 trial (NCT06058039) in MDD. The primary endpoint was the change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Neumora projected the job cuts would save it approximately $10 million annually, to be partially offset this year by approximately $2 million in one-time restructuring costs. Neumora said current cash and cash equivalents are expected to provide runway into Q3 2027, including multiple expected key clinical milestones. Neumora’s pipeline includes NMRA-511 in Alzheimer’s disease agitation, NMRA-898 in schizophrenia, and NMRA-215 in cardiometabolic disease.
- uniQure (Nasdaq: QURE) shares zoomed 78% from $26.99 to $48.16 Wednesday after the gene therapy developer announced the FDA’s revised position that a three-year analysis from its two-trial, Phase I/II study (United States, NCT04120493, and Europe (NCT05243017) of AMT-130 in Huntington’s disease was now acceptable as the primary basis of a Biologics License Application (BLA) for accelerated approval of the gene therapy. Researchers hailed “game-changing” data last year showing significant slowing of Huntington’s disease (HD) progression, but the FDA disagreed while its Center for Biologics Evaluation and Research (CBER) was headed by Vinayak (Vinay) Prasad, MD, who resigned in April. uniQure said the FDA seeks to align on the confirmatory study design prior to the BLA submission, including considering allowing concurrent control on standard-of-care therapy instead of a sham procedure. “FDA communicated that they would work as expeditiously as possible with uniQure on this effort. The company is committed to conducting the confirmatory study without delay and expects to further align with the FDA on the details of such a study prior to BLA submission,” uniQure stated.
The post StockWatch: Positive Phase III Data Sells Investors on Intellia appeared first on GEN – Genetic Engineering and Biotechnology News.
<![CDATA[Explore how circadian gene rhythms differ in schizophrenia, depression, and bipolar disorder—and why stable sleep timing may curb addiction risk.]]>
Turning Rejection Into a Roadmap: Advice for the Next Generation of Mental Health Leaders
A Conversation with Tom Osborn, Founder of Africa’s Largest Mental Health Provider Shamiri Institute
Aaliyah Nadirah Madyun, program director at the Stavros Niarchos Foundation (SNF) Global Center for Child and Adolescent Mental Health at the Child Mind Institute, recently sat down with Tom Osborn, founder of the Shamiri Institute and an International Advisory Board member at the SNF Global Center. They discussed Osborn’s remarkable journey as a young entrepreneur.
At just 18, while studying at Harvard University, Osborn founded the Shamiri Institute, which has since grown into Africa’s largest youth mental health provider — now reaching over 100,000 young people annually and having trained and employed more than 3,000 providers. In this candid conversation, Osborn shares hard-won lessons on resilience, mentorship, and well-being. He offers advice to the SNF Global Center’s Youth Council members — many of whom are launching their own mental health initiatives in communities across Greece, Brazil, South Africa, and beyond.
AM: You founded Shamiri when you were just 18. Many members of our SNF Global Center Youth Councils are now launching their own mental health organizations. What advice would you give them?
TO: I think these past three to five years post-COVID have been quite good for mental health. There’s just more dialogue, more conversation. It’s maybe one of the best times to start working in mental health. There is a big space for young people to be leaders. On the other hand, it’s also very difficult.
AM: What kind of difficulties can young people expect to encounter?
TO: It’s very difficult for a few reasons. We normally start this work because we have a lot of passion, enthusiasm, and commitment to the cause. But that is not the day-to-day of being a social entrepreneur. It’s convincing people to partner with you, to fund you, etc., which is a completely different skill set to learn. And the second part is getting a level of comfort with failure. Because the reality is, on average, nine out of ten doors that you try to open will not open; especially when you are starting. For example, if you’re in Brazil and there are 100 other young people trying to start something, there is a finite pool of opportunities and resources. So, when you are starting, part of the initial process requires you to develop resilience and a growth mindset.
AM: Could you speak about the role mentorship has played in your journey, and how young entrepreneurs can leverage mentorship to navigate the challenges of building something from the ground up?
TO: Mentorship is really crucial. Finding folks — researchers, practitioners, or just folks in the community — who can help provide guidance as you build the skills you need to be an effective entrepreneur.
AM: How would you recommend young people go about finding a mentor? It seems like that ability, identifying and cultivating a mentoring relationship, might be a skill set in itself.
TO: In my experience, there are three pathways. In many countries we have what we call accelerators, which look for young people who literally have an idea and enthusiasm, and then take them through 10–16 weeks of bootcamp where they can learn the skills to develop their idea. So, that’s one pathway. The second pathway, which really worked for me but may sound intimidating, is direct outreach to folks who have done something similar. So, you can do some research. It doesn’t have to even be related to mental health. It can be education or some broader thing. But find someone who has built something that you admire. You will be surprised how many people are willing to support and pay it forward, because we all have benefited from the help of someone else. I created an Excel spreadsheet with a list of people who I looked up to, and I reached out to them on LinkedIn. Sometimes you can even find their email. Some people said “no”, but if you reach out to 10 or 20 people, some people will talk to you. And the third pathway is . . . increasingly we have a lot of resources like the SNF Global Center Youth Councils and international organizations that deal with mental health. You can join these organizations to expand your network.
AM: Could you share your story with us and tell us how you got started?
TO: I started when I was in University as part of a research project I was doing when I was studying psychology. I needed to do something for my thesis and in the process of doing that I applied to an accelerator. I also went to my professor and asked him, ‘Do you know anyone who could connect me with?’ In fact, he helped me write my first grant and gave me the opportunity to learn those entrepreneurial skills.
AM: Starting at such a young age, one can imagine that you must have encountered many challenges and setbacks. What were the key lessons you took away from that growth period?
TO: The reality of this work, and not to discourage people but to give a factual picture, is that there are more setbacks than there are wins. Part of the process is that you learn from the setbacks. I can give you an example of some of my own setbacks. In my first year of doing this, we tried to raise money. We applied for grants, sent out proposals, etc.; but we couldn’t raise any money. So, what I did after getting the rejection is I would email and ask, “Do you have any feedback for us about why we didn’t get the funding?” or “Can we jump on a call so you can explain what we can do better?” What I learned from that was the way I was communicating what we were doing made sense in my mind, but I wasn’t putting myself in the shoes of the person who was reviewing the proposal. I only have five to ten minutes of someone’s time. So, how can I really simplify my message? For example, my first proposal was, “Shamiri does task-shifting mental health interventions for adolescent depression, anxiety, etc.” If you are in the field, you maybe get it. But if you are somebody who is just reading grants on mental health education, you don’t really get it. Now we say, “Shamiri means thrive and we enable young people to thrive.” So that invites people to ask how we’re helping people to thrive.
AM: What is another setback that surprised you?
A second example of a failure is getting buy-in from the beneficiaries that we were trying to work with. I thought, “We have this great idea, we’ve done this research, and it works. We’re going to go to schools and they’re going to be like, ‘This is great! Come work with us.’ Teachers are going to want to work with us.” But actually, in our first three years we were trying to work with 25,000 students and we ended up working with only 1,000 students. We really struggled with getting people to sign up. The lesson from that was we were thinking more from the idea this was our product, rather than thinking, “What is the problem that I am trying to solve for this person?” To give a concrete example, there are three people we need to get buy-in from: young people in schools, teachers, and parents. Just having a great product does not mean that people are going to use it. You need to figure out what the problem is. How can I solve it? How do I communicate this to users?
AM: I can imagine that dealing with failures and setbacks is extremely hard, especially for a young person. What would you say to a young person who is currently experiencing this?
TO: Finding ways to stay grounded and healthy from a well-being perspective is really crucial. Identify what matters to you and connect with those things. And ideally if you can find a way to build a routine around that, it could help. Doing this work takes a big toll. If you don’t find ways to ground yourself and get the energy to continue with this, you may burn out.
AM: Do you have some final words for our Youth Council members and other young people reading this?
TO: Those closest to the problem are those closest to the solution. I am from Kenya, which is a really young country. The median age is 19 and 70 percent of the population is under 30. If we are to solve some of these pressing problems, including mental health, those solutions are going to have to come from young people.
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