Tag: Denmark

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Malaria Drug Reveals Genetic Vulnerability Across Cancers

Scientists have found that the antimalarial drug quinacrine can exploit a vulnerability in cancers that become reliant on the NDRG1 protein to sustain their DNA damage response. Published in Science Signaling, their study not only identifies NDRG1 as a promising therapeutic target, but also demonstrates a new strategy for discovering similar vulnerabilities across multiple types of cancer.

“Our findings suggest that NDRG1 expression could serve as a biomarker to help identify patients most likely to benefit from therapies targeting this pathway,” said Garik V. Mkrtchyan, PhD, assistant professor at the University of Copenhagen and lead author of the study. “We further showed that high NDRG1 expression predicts poor survival across multiple cancers, and that inhibiting NDRG1 creates vulnerabilities, highlighting new opportunities for precision oncology.”

Mkrtchyan and colleagues set out to identify new targets for cancer therapeutics by leveraging the concept of synthetic lethality—a phenomenon where cancer cells can survive the loss of one of two genes but die when both are inhibited. This approach has already proven successful in ovarian, breast, and prostate cancers with BRCA mutations, which are particularly vulnerable to PARP inhibitor drugs. 

“In oncology, this concept is particularly promising because cancer cells often harbor mutations in specific DNA damage response pathways, making them highly dependent on the remaining repair mechanisms for survival,” said Mkrtchyan. “Targeting these dependencies enables selective elimination of cancer cells while sparing healthy tissue.”

Using transcriptomics data, the researchers identified quinacrine as a promising candidate for disrupting the DNA damage response by targeting the stress-response protein NDRG1. Quinacrine has been used as an antimalarial drug for nearly a century, later gaining approval as a treatment for lupus. In recent years, the compound has attracted growing interest as a potential cancer treatment. 

Screening through hundreds of cancer cell lines revealed that blood cancers, which generally showed high NDRG1 expression, were the most sensitive to the drug. Colorectal cancer cells were also sensitive to quinacrine, especially those with mutations in the MLH1 and PARP3 genes. The team later confirmed these findings in patient datasets, where high NDRG1 expression together with loss of either of these genes correlated with improved survival rates. 

“While quinacrine has previously been reported to possess anticancer activity, our study uncovers upstream mechanisms of its action on DNA damage response,” said Mkrtchyan. “By applying an automated robotics screen across more than 130 cancer cell lines, we identified novel synthetic lethal interactions involving NDRG1, providing a framework for discovering new therapeutic vulnerabilities across multiple cancer types.”

Despite its potential as a cancer therapy, quinacrine can potentially cause unwanted side effects. The researchers therefore plan to explore alternative drug candidates that can inhibit NDRG1 with more potency while reducing toxicity.

“The next steps will be to develop small molecules that inhibit NDRG1 with greater potency and specificity than quinacrine, thereby minimizing potential off-target effects,” said Mkrtchyan. “From a translational perspective, we aim to validate the identified synthetic lethal interactions in preclinical tumor models and investigate whether targeting the NDRG1 axis can overcome treatment resistance across a broader range of cancers.”

The post Malaria Drug Reveals Genetic Vulnerability Across Cancers appeared first on Inside Precision Medicine.

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HALO-TRIAL: High, Medium And LOw Intensity Psychotherapy for Binge Eating Disorder

Conditions: Binge Eating Disorder; Binge Eating Episodes; Binge Eating/Loss of Control Eating; Binge Eating Disorders; Binge Eating; Binge Eating Behaviour; Binge Eating Disorder Associated With Obesity; Eating Disorder Binge; Eating Disorders

Interventions: Behavioral: Cognitive Behavioral Therapy Enhanced – Individual; Behavioral: Cognitive Behavioral Therapy Enhanced – Group; Behavioral: Cognitive Behavioral Therapy – Guided Self Help; Behavioral: Systemic Narrative Therapy – Group

Sponsors: Herlev and Gentofte Hospital; Jascha Fonden; BETA-HEALTH Foundation; Mental Health Centre Ballerup; Region Capital Denmark; University of Copenhagen

Recruiting
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The ECHO study: compassion-focused therapy for young voice hearers and their caregivers. A pilot study

BackgroundVoice hearing can occur in healthy people without a trigger, be caused by a traumatic event, or occur as part of a psychiatric disorder. There are still many gaps in our understanding of voice hearing, and research in this field can be challenging, maybe because it is associated with shame and stigma. Those who experience distress by voice hearing could benefit from a treatment, aimed directly at that. The ECHO manualized treatment is based on the principles of compassion-focused therapy (CFT).MethodsTreatment will take place on several different psychiatric hospitals in the Region of Southern Denmark. Treatment consists of a 10-session, manualized CFT for voice hearing. Caregivers participate in half of the sessions, and a recording of the voice content is made, which the caregivers are encouraged to listen to. The study is designed as a prospective single-arm pre–post intervention study using a mirror-image approach, in which participants serve as their own controls over time. The intervention group consists of (N = 60) voice-hearing adolescents aged 13–18 years. Additionally, a clinical comparison group (who also receive the intervention) of (N = 20) individuals aged 18–20 years with first-episode schizophrenia and voice hearing is included for descriptive and exploratory analyses. Data are collected 3 months prior to CFT treatment, immediately before the start of treatment, immediately after treatment is completed, and at 1 month follow-up. Data will be centered around social cognition, perceived social safeness, social connectedness, general well being, auditory hallucinations and compassion.DiscussionThe ECHO study addresses the wellbeing and thriving of an overlooked group of young people. The results of this study will provide information about who the voice hearers are, what challenges they face, and how they perceive them. The results will also provide information about the feasibility and efficacy of the treatment manual and, thus, its potential further implementability. Caregivers participate in half of the sessions, to facilitate a common language about mental states and voice hearing. To support their understanding, a recording of the voice content is made and the caregivers are encouraged to listen to it. We suggest that when caregivers understand the young voice hearers’ experiences, they can adjust their expectations and approach accordingly. We also suggest that by sharing the voice content, the young voice hearer will feel less isolated.Study protocol registrationhttps://clinicaltrials.gov/study/NCT07314515, identifier NCT07314515.
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Engineered AAVs Harness Glymphatic System to Reach Brain Targets in Mice

Crossing the blood-brain barrier and avoiding off-target effects are two important challenges for gene therapies designed to target diseases of the brain. Now, developers of a gene therapy delivery platform that pairs specially engineered adeno-associated viruses (AAVs) with a delivery strategy that harnesses the brain’s fluid transport pathways claim that their approach addresses both issues and could help pave the way to new treatments for neurological disorders like multiple sclerosis, Huntington’s disease, and rare pediatric white matter disorders. 

Details of the work were published recently in a Nature Biotechnology paper titled “Efficient targeting of human glial progenitor cells in vivo with engineered AAV vectors and glymphatic delivery.” The research was done by scientists at University of Rochester Medicine and the University of Copenhagen. 

While the platform can deliver therapeutic genes broadly throughout the brain, it preferentially targets human glial cells. Steve Goldman, MD, PhD, lead author of the study and co-director of the Center for Translational Neuromedicine at URochester, has spent his career studying glial cells and elucidating their role in disease progression and recovery. Previously, his lab developed human glial progenitor cell models and investigated the link between glial dysfunction and neurological disease. For example, in Huntington’s disease, his lab has shown that healthy human glial progenitor cells could outcompete and replace diseased cells in the brain. 

“Over the last decade, we’ve learned that many neurological disorders involve glial dysfunction as a major driver of disease,” Goldman said. “That realization has created an urgent need for tools that can safely and efficiently deliver therapies to these cells throughout the brain.”

The current study gets scientists one step closer to that goal. Digging into the details, Goldman and his colleagues engineered a library of modified AAV5 viral vectors by making small changes to the vectors’ capsids. They then screened the vectors in mice whose brains were transplanted with human glial progenitor cells and tracked their movements to identify which ones most effectively infected the human glial progenitor cells and their descendants including astrocytes and oligodendrocytes. 

“Human cells display different molecular signatures than mouse cells, and cells behave differently in the brain than they do in a dish,” Goldman explained. “By selecting vectors under biologically relevant conditions, we were able to identify candidates with a strong preference for human glia.”

Next, the team turned their efforts to studying how best to distribute the AAVs throughout the brain. For that, they turned to the glymphatic system, the brain’s network of fluid-filled pathways used to clear metabolic waste by circulating cerebrospinal fluid through the brain. They delivered the engineered AAVs into the cisterna magna, a fluid-filled compartment at the base of the brain, while using hypertonic treatment to enhance fluid uptake into the network. This approach spread the vectors broadly throughout the brain tissue while largely avoiding the blood-brain barrier, and reducing exposure to peripheral organs like the liver. 

“The glymphatic system is changing the way we think about brain drug delivery,” Goldman said. “Rather than trying to force therapies across the blood-brain barrier from the bloodstream, we can use the brain’s own transport pathways to distribute them more effectively where they are needed.”

Immediate targets for this approach are pediatric lysosomal storage diseases and other inherited disorders in which glial cells lack critical enzymes. Essentially, diseases of the brain’s white matter with well-defined biological targets. Further down the road, the approach could support novel therapies for multiple sclerosis, age-related white matter loss, and Huntington’s, among other neurodegenerative disorders where glial dysfunction is involved.

“We envision a future in which vectors can be designed for specific diseases and specific cell populations,” Goldman said. His lab is already exploring whether they can use artificial intelligence to design viral capsids that have specific targeting characteristics. “This study shows that by combining targeted vector engineering with glymphatic delivery, we can begin to build that future.”

The post Engineered AAVs Harness Glymphatic System to Reach Brain Targets in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.

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Top 10 Best-Selling Drugs 2026

Thanks to booming sales of blockbuster obesity and diabetes treatments, the amount that Americans spent on prescription drugs this year is on track to surpass $1 trillion, according to a report released in April by the American Society of Health-System Pharmacists (ASHP).

That would be a sharp, above-inflation 9.3% increase from the $915 billion in U.S. drug sales recorded last year, one of the fastest one-year percentage jumps ever recorded by the group. That 12.7% jump is higher than the one-year increases achieved by healthcare costs, and growth in the overall economy.

Even more eye-opening: Nearly one-third of prescription drug spending growth came from the $132 billion spent on a single category, namely glucagon-like peptide 1 (GLP-1) receptor agonists indicated for obesity/wight management and for type 2 diabetes.

“GLP-1s have fundamentally reshaped the drug-spending landscape,” Eric Tichy, PharmD, MBA, lead author of the report and division chair of supply chain management at Mayo Clinic. “And we are still on the steep part of the curve.”

According to ASHP, the 2025 and projected 2026 leaps in drug spending reflect more medications being used by more patients, with spending growth being predicted to range from 10–12% overall.

That would appear to explain the robust increases in sales by every one of the top 10 best-selling prescription drugs (based on 2025 sales) featured in this GEN A-List. Top-selling drugs are ranked based on sales or revenue reported for 2025 by biopharma companies in press announcements, annual reports, investor materials, and/or conference calls. Each drug is listed by name, sponsor(s), 2025 sales, 2024 sales, and the percentage change between those years.

The total 2025 aggregate value of the top 10 best-selling drugs was $188.136 billion, up 21.5% from $154.888 billion in 2024—and more than double (up 127.5% over 10 years from the $82.694 billion generated by 2016’s top 10 sellers, as reported by GEN.

Just missing the top 10 at #11 was Novo Nordisk’s Wegovy®, the glucagon-like peptide 1 (GLP-1) receptor agonist indicated for weight loss in obese or overweight adults. Treatments ranked number 11 through number 15 in 2025 generated between approximately $8.4 billion and $12.2 billion in revenues. In addition to Wegovy, best sellers Nos. 12-15 include:

  • Opdivo® and its subcutaneous injection version Opdivo Qvantig™ (nivolumab / nivolumab and hyaluronidase-nvhy), marketed by Bristol Myers Squibb (BMS) worldwide except Japan, South Korea, and Taiwan, where Ono Pharmaceutical markets the drug.
  • Trikafta® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) from Vertex Pharmaceuticals, which markets the drug outside the U.S. as Kaftrio®.
  • Ocrevus® (ocrelizumab) from Roche and its U.S. subsidiary Genentech.
  • Farxiga® (dapagliflozin), from AstraZeneca, which markets the drug outside the U.S. as Forxiga®

Three drugs that ranked between #11 and #15 on last year’s A-List based on 2024 sales placed lower this year: Eylea/Eylea HD (aflibercept) from Regeneron Pharmaceuticals and Bayer, which ranked No. 17 in 2025 sales; Gardasil/Gardasil 9 (Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant/Human Papillomavirus 9-valent Vaccine, Recombinant) from Merck & Co., now No. 27; and Humira® (adalimumab) from AbbVie, which had long been the top-selling drug for years until being surpassed by Keytruda® but is now No. 32.

Eylea and Humira now face competition from biosimilars, while Merck halted Gardasil shipments to China last year, citing declining sales.

 

1. Keytruda® / Keytruda Qlex™ 1

(pembrolizumab / pembrolizumab and berahyaluronidase alfa-pmph) Merck & Co.

2025 Sales: $31.680 billion 1

2024 Sales: $29.482 billion

% Change: +7.5%

 

2. Mounjaro®

(tirzepatide) Eli Lilly

2025 Sales: $22.965 billion

2024 Sales: $11.540 billion

% Change: +99.0%

 

3. Eliquis®

(apixaban) Bristol Myers Squibb and Pfizer

2025 Sales: $22.404 billion ($14.443 billion BMS + $7.961 billion Pfizer)

2024 Sales: $20.699 billion ($13.333 billion BMS + $7.366 billion Pfizer)

% Change: +8.2%

 

4. Ozempic®

(semaglutide) Novo Nordisk

2025 Sales: $19.611 billion (DKK 127.089 billion)

2024 Sales: $18.570 billion 2 (DKK 120.342 billion)

% Change: +5.6%

 

5. Dupixent®

(dupilumab)3 Sanofi and Regeneron Pharmaceuticals

2025 Sales: $18.124 billion (€15.714 billion)

2024 Sales: $15.077 billion 4 (€13.072 billion)

% Change: +20.2%

 

6. Skyrizi®

(risankizumab-rzaa) AbbVie

2025 Sales: $17.562 billion

2024 Sales: $11.718 billion

% Change: +49.9%

 

7. Darzalex® / Darzalex Faspro®

(daratumumab / daratumumab and hyaluronidase-fihj) Johnson & Johnson and Genmab 5

2025 Sales: $14.351 billion 5

2024 Sales: $11.670 billion 5

% Change: +23.0%

 

8. Biktarvy®

(bictegravir, emtricitabine, and tenofovir alafenamide) Gilead Sciences

2025 Sales: $14.334 billion

2024 Sales: $13.423 billion

% Change: +6.8%

 

9. Jardiance family

(empagliflozin, monotherapy and in combinations with linagliptin and metformin) 6 Boehringer Ingelheim and Eli Lilly

2025 Sales: $13.563 billion ($10.132 billion [€8.785 billion] Boehringer Ingelheim + $3.431 billion Eli Lilly] 6

2024 Sales: $12.979 billion ($9.638 billion [€8.357 billion] Boehringer Ingelheim + $3.341 billion Eli Lilly) 6

% Change: +4.5%

 

10. Zepbound®

(tirzepatide) Eli Lilly

2025 Sales: $13.542 billion

2024 Sales: $4.926 billion

% Change: +174.9%

 

References

  1. Starting in 2025, Merck combined into a single figure the sales of Keytruda (pembrolizumab) and Keytruda Qlex™, a subcutaneous injectable immunotherapy consisting of pembrolizumab and berahyaluronidase alfa, and which like Keytruda is indicated to treat multiple types of cancer.
  2. Figure differs from the $18.655 billion reported by GEN in last year’s A-List of Top 10 Best-Selling Drugs due to currency fluctuations.
  3. Sanofi records global net product sales of Dupixent, with each company recording its half-share of profits on global sales of the drug.
  4. Figure differs from the $15.125 billion reported by GEN in last year’s A-List of Top 10 Best-Selling Drugs due to currency fluctuations.
  5. All sales figures are recorded by Johnson & Johnson, with Genmab receiving royalties on worldwide sales from J&J. Genmab does not disclose specific royalty revenues for Darzalex and Darzalex Faspro but has furnished a 2025 royalty figure for the treatments of $2.443 billion, up 12.5% from DKK 13.922 billion ($2.172 billion) in 2024. Genmab changed its reporting and functional currency to U.S. dollars from Danish kroner as of 2025.
  6.  Lilly includes revenues from Glyxambi® (empagliflozin/linagliptin), Synjardy® (empagliflozin/metformin hydrochloride), and Trijardy® XR (empagliflozin, linagliptin, and metformin hydrochloride) in its revenue figures for the Jardiance family—which includes net product revenue as well as collaboration and other revenue.
  7.  Figure differs from the $12.832 billion in 2024 sales reported by GEN in last year’s A-List of Top 10 Best-Selling Drugs due to currency fluctuations.

The post Top 10 Best-Selling Drugs 2026 appeared first on GEN – Genetic Engineering and Biotechnology News.

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iCARE Self-Guided Digital Intervention for Postpartum Depression in Danish Mothers: Formative Research Using User-Centered Design

<strong>Background:</strong> Postpartum depression (PPD) is a major public health concern. Despite advancements in treatment, many barriers to accessing care remain. There has been a growing interest in digital interventions for the prevention and treatment of PPD. However, for mothers with mild and moderate symptoms of depression, there is a limited offer of self-guided internet-based interventions developed with user input and with considerations on how to integrate the intervention into stepped care models for PPD. <strong>Objective:</strong> The aim of this study was (1) to describe the process of the design and development of iCARE, a self-guided digital psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark, (2) present the program’s theory illustrated by a logic model, and (3) explore its initial usability and prospective acceptability. <strong>Methods:</strong> Applying user-centered design methods, the intervention development followed six steps: (1) a literature review to identify evidence‑based therapeutic components of self‑guided interventions for PPD, (2) interviews with women with lived experience of PPD and group discussions with mental health experts and home‑visiting providers to identify user needs, (3) iterative design and content development with stakeholder feedback in collaboration with the Department of Digital Psychiatry, (4) prototype testing using think‑aloud usability sessions and interviews with 5 mothers, (5) a group cognitive walkthrough with mental health experts, and (6) final refinement and implementation of the iCARE program with developers and designers. <strong>Results:</strong> Initial interviews with mothers and maternal health care providers emphasized the importance of a digital intervention offering timely psychoeducation, coping strategies, and pathways to in-person care while addressing the diversity of expressions of PPD symptoms. Stakeholders recommended a flexible program, multimodal content, and integration into maternal care systems with community health nurses supporting engagement and participation. The prototype was designed to be user-centered, engaging, and with multiple interactive features. It included components on psychoeducation, cognitive exercises grounded in cognitive behavioral therapy, acceptance and commitment principles, and mood-monitoring. The prototype was designed to be user-centered and engaging, with interactive features and components on psychoeducation, cognitive exercises grounded in cognitive behavioral and acceptance and commitment principles, and mood-monitoring. Prototype testing indicated high prospective acceptability and led to refinements across 6 themes: appropriateness of content; motivation and engagement; inclusivity and gender representation; clarity of instructions and data use; understanding of therapeutic method; and usability, layout, and navigation. <strong>Conclusions:</strong> iCARE is a self-guided internet-based psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark. It was developed with user input by using qualitative methods, user-centered design, and psychological theory. Further research is needed to evaluate the feasibility and effectiveness of the program in a randomized controlled trial and its integration into maternal health care models such as universal PPD screening and home-visiting.
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StockWatch: enGene Shares Crater on Declines in Complete Response Rates to Bladder Cancer Therapy

enGene (NASDAQ: ENGN) stock suffered an 83% plunge this past week that reflects just how competitive the field is among drug candidates for nonmuscle invasive bladder cancer (NMIBC)—and how questions over clinical data are enough to send investors scurrying to sell their shares.

enGene shares cratered 81% Thursday from $8.85 to $1.72, then fell another 13% Friday, reaching a 52-week low as it finished the week at $1.50.

The sharp falloff followed enGene reporting updated data from its Phase II LEGEND trial (NCT04752722) assessing its nonviral gene therapy candidate detalimogene voraplasmid in high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC patients with carcinoma in situ (CIS) with or without concomitant papillary disease (CIS±papillary). The data showed a drop in response rates from a November 2025 readout, falling short of company and Wall Street expectations.

As of the April 21 data cutoff, 67 of 124 evaluable patients treated with detalimogene (formerly EG-70) achieved a 54% complete response (CR) at any time, a rate that fell to 43% (52 of 121 evaluable patients) CR rate at six months. That compares with the 63% CR at any time and 62% CR rate at six months shown for the first 62 patients assessed, as announced by enGene in November 2025.

Also, detalimogene showed a nine-month CR rate of 32.7%, which fell to 13.3% at 12 months after treatment. Engene said it will present its data at the American Urological Association Annual Meeting (AUA 2026), set for May 15–18 in Washington, DC.

“While durability outcomes to date are not what we hoped, these data are preliminary,” enGene president and CEO Ron Cooper stressed in a statement. “We are focused on evaluating the totality of the data as it evolves and plan to continue to engage with the FDA and the medical community.”

Speaking to analysts, Cooper added: “The data are not yet fully mature, and the durability picture is incomplete. We plan to await longer-term durability data for all of Cohort 1 in the second half of the year and continue our ongoing discussion with the FDA regarding both our statistical analysis plans and plans for potential BLA filing.”

“Below key benchmarks”

At least two analysts warned that the updated data will make it harder for enGene to compete with other developers of NMIBC treatments now in the clinic.

“Durability now screens below key benchmarks in the setting, which makes it hard for us to underwrite meaningful commercial upside for detalimogene in what will be a crowded mkt, where ~40% 12‑mo CR is the bar to clear,” cautioned Maury Raycroft, PhD, equity analyst with Jefferies, in a research note.

Raycroft slashed enGene’s 12-month price target 82% from $28 to $5. More ominously, Raycroft chopped Jefferies’ peak sales forecasts for detalimogene by 79%—from the $1.7 billion forecasted for the gene therapy across CIS±papillary, papillary‑only, and BCG‑naïve NMIBC, to $350 million for CIS±papillary alone.

The NMIBC treatment space has expanded in recent years as established drugs like the cancer immunotherapy blockbuster Keytruda® (pembrolizumab), marketed by Merck & Co. (NYSE: MRK), have been joined on the market by newer therapies.

One is Johnson & Johnson (NYSE: JNJ)’s Inlexzo™ (gemcitabine), an intravesical drug releasing system (iDRS) designed to provide sustained local delivery of a cancer treatment into the bladder. Two other newer therapies are Adstiladrin® (nadofaragene firadenovec-vncg), a nonreplicating adenoviral vector-based gene therapy indicated for high-risk BCG-unresponsive NMIBC with CIS±papillary and marketed by privately held Ferring Pharmaceuticals (which licensed the drug from another private company, FKD Therapies, in 2018); and ImmunityBio (NASDAQ: IBRX)’s interleukin-15 (IL-15) receptor agonist Anktiva® (nogapendekin alfa inbakicept-pmln), indicated with BCG. ImmunityBio is part of the privately held NantWorks portfolio of companies.

Those marketed drugs are expected to be joined over the next couple of years by candidates being developed by:

  • CG Oncology (NASDAQ: CGON), which is expected to report topline data from the Phase III PIVOT-006 trial (NCT06111235) of cretostimogene grenadenorepvec, also called CG0070, as an adjuvant therapy in intermediate-risk NMIBC. First results on the combo of cretostimogene with gemcitabine from the Phase II CORE-008 trial (NCT06567743) are to be presented at AUA 2026.
  • Relmada Therapeutics (NASDAQ: RLMD), which will present two abstracts focused on its NDV-01, a sustained-release intravesical formulation of gemcitabine and docetaxel being developed to treat NMIBC at AUA 2026. Relmada plans to present nine-month complete response data from its open-label Phase II trial (NCT06663137) assessing NDV-01 in high-risk NMIBC, as well as discuss its open-label Phase III BOOST trial (NCT07313891), which is evaluating NDV-01 vs. surveillance following transurethral resection of bladder tumor (TURBT).

Mani Foroohar, MD, senior managing director, genetic medicines, and a senior research analyst with Leerink Partners, noted that enGene’s 54% any time and 43% six-month updated CR rates lagged behind those of three competitors: Anktiva (71% and 56%), cretostimogene (75.5% and 64%), and Inlexzo (82% and 59%). However, he added that Adstiladrin was more comparable to detalimogene, which showed rates of 51% and 41%.

Competitive position concern

“Weaker data in recent patient cohorts and lower-than-expected durability trends undermine our confidence in [detalimogene]’s competitive position and essentially foreclose the possibility of closing the efficacy gap with CGON, JNJ, etc., in a later LEGEND update,” Foroohar wrote in a research note.

“With shares trading at a level pricing in program failure, investor focus will center on cohort consistency, data evolution with longer follow-up, and FDA interpretation of the totality of the dataset (questions that will take time to address and will not be resolved prior to full LEGEND data/subsequent regulatory engagement,” Foroohar added.

Like Raycroft, Foroohar also now projects $350 million in unadjusted peak year sales for detalimogene, shredding his firm’s projection by 65% from $1 billion.

“From here, investor discussion will center on whether longer follow-up and additional cohort maturation can stabilize efficacy trends ahead of further FDA engagement in 2H26.”

enGene and Cooper insist that detalimogene is more than up to the challenge of competing with other NMIBC treatments. Of the 52 patients who responded at six months, 37 of 44 patients who had a nine-month assessment were in CR (an additional eight patients are pending evaluation), while 13 of 22 patients who had a 12-month assessment were in CR (an additional 11 patients are pending evaluation).

Among patients who showed the 43% six-month CR rate, 14% (6 of 43) successfully converted from non-CR to CR post re-induction.

The company cited other data from the LEGEND trial showing that the progression rate to muscle-invasive or advanced disease was 3.2%, a figure enGene calls low. Detalimogene was generally well tolerated, the company added, with 55% of patients having experienced a treatment-related adverse event (TRAE), mostly mild (Grade 1 and 2), though six patients (4.8%) reported a Grade 3 TRAE.

“These updated data continue to reinforce the favorable safety and tolerability profile of detalimogene and its clinical activity in a heavily pretreated, high-risk NMIBC patient population with limited therapeutic options,” enGene’s Cooper stated. “Importantly, the low rate of progression to muscle-invasive disease leaves patients eligible for other bladder-sparing therapies.”

Detalimogene’s favorable safety profile was also acknowledged by Jefferies’ Raycroft: “We continue to view this administrability/safety profile as a core differentiator vs other intravesical gene/immune constructs (and a key adoption lever), even as durability to date is tracking below expectations.”

IPO roundup: Odyssey raises $304M, drops 9%

Odyssey Therapeutics (NASDAQ: ODTX) raised $304 million in gross proceeds through an upsized initial public offering (IPO) by selling 15.5 million shares priced Thursday at $18 a share, the top of its $16–$18 range, and well above the 13.2 million shares it disclosed in its prospectus just before the offering. Concurrently, an affiliate of TPG Life Sciences Innovations purchased 1.39 million shares at the IPO price, raising another $25 million for Odyssey.

But on their first full day of trading on Friday, Odyssey’s shares fell 9%, closing at $16.42, as investors deemed the upsizing to be aggressive.

Odyssey, a developer of targeted therapies for autoimmune and inflammatory diseases, said it would use approximately $135 million in IPO proceeds to advance its lead candidate, the oral small molecule RIPK2 scaffolding inhibitor OD-001, through 12-week induction readouts from its planned Phase IIa combination trial and Phase IIb monotherapy trial in ulcerative colitis.

Plans also call for using approximately $50.0 million of proceeds to advance Odyssey’s oral small molecule SLC15A4 inhibitor OD-002 through IND-enabling activities and a planned Phase I/IIa trial; and the rest for additional discovery, preclinical, and clinical activities for disclosed or future programs, enabling capabilities, as well as general corporate purposes, working capital, and other capital expenditures.

An option to purchase up to an additional 2.325 million shares at the IPO price is held by Odyssey’s IPO underwriters: J.P. Morgan, TD Cowen, and Cantor are joint book-running managers, while Wedbush PacGrow and Oppenheimer are co-lead managers.

The Odyssey IPO is one of four biotech IPOs emerging in recent weeks:

  • Hemab Therapeutics Holdings (NASDAQ: COAG), based in Cambridge, MA, and Copenhagen, closed its IPO on May 4, having raised $346.7 million by selling 19,262,500 shares at $18 a share—the original offering of 16.75 million shares, plus all 2,512,500 shares for which underwriters held purchase options. Goldman Sachs, Jefferies, and Evercore ISI were joint book-running managers; Wedbush PacGrow was the lead manager. Shares have since jumped 40%, closing Friday at $25.12.
  • Seaport Therapeutics (NASDAQ: SPTX) of Boston garnered $254.88 million on April 30 by selling 14.16 million shares at $18 a share. Seaport’s underwriters have a 30-day option to buy an additional 2.124 million shares at the IPO price less underwriting discounts and commissions. Goldman Sachs, J.P. Morgan, Leerink Partners, Citigroup, and Stifel are joint book-running managers. Shares have since slipped 11%, closing Friday at $16.05.
  • A day earlier, Avalyn Pharma (NASDAQ: AVLN), also of Boston, launched an IPO that garnered $300 million by selling 16,666,667 shares at $18 a share—and revived the market of biotech initial offerings after a lull during March and early April. Avalyn ultimately racked up $345 million in gross proceeds after its underwriters exercised in full their option to buy 2.5 million more shares at the IPO price. Morgan Stanley, Jefferies, Evercore ISI, and Guggenheim Securities were joint book-running managers. Shares have since vaulted 52%, closing Friday at $27.33.

Leaders and laggards

  • Atara Biotherapeutics (NASDAQ: ATRA) shares nearly doubled, leaping 92% from $5.15 to $9.93 Thursday after saying its partner Pierre Fabre Pharmaceuticals (PFP) had a productive Type A meeting with FDA officials to discuss an approval path for tabelecleucel (tab-cel). PFP’s Biologics License Application (BLA) has been rejected twice by the agency through Complete Response Letters, the most recent one in January. The FDA, Atara said, agreed that a single-arm study with an “appropriate” historical control, conducted in a pre-specified manner, “could serve as an adequate and well-controlled study and provide safety and efficacy data in support of a future marketing application.” Atara said PFP intends to submit updated data with longer follow-up from the pivotal Phase III ALLELE trial (NCT03394365) assessing tabelecleucel in adults and children ages 2+ with relapsed/refractory Epstein-Barr virus plus post-transplant lymphoproliferative disease (PTLD) following solid organ transplant or hematopoietic cell transplant.
  • Entrada Therapeutics (NASDAQ: TRDA) shares nosedived 57% Thursday from $16.03 to $6.85 after the genetic medicine developer reported topline data from Cohort 1 of the multiple ascending dose (MAD) portion of the Phase I/II ELEVATE-44-201 trial (NCT07037862) that the company called positive, but which disappointed investors. Entrada said its Duchenne muscular dystrophy (DMD) candidate ENTR-601-44 met the trial’s primary objective by showing favorable safety and tolerability, no discontinuations, and no serious adverse events. But data showed an increase of 2.36% in dystrophin from a baseline of 4.00%—compared to the 10% increase sought by analysts such as Myles R. Minter, PhD, of William Blair. “Management is attributing the miss on biomarker data to lower-than-expected drug exposure,” Minter wrote, “likely due to the transition from dosing adults to juvenile patients.” Entrada cited other positive data, such as lower plasma exposure in Cohort 1 participants ages 6–17 vs. healthy adult volunteers; and markers of kidney function via eGFR, Cystatin C, and magnesium all falling within normal ranges and comparable to placebo.
  • Moderna (NASDAQ: MRNA) shares rose 12% Friday from $48.54 to $54.35 after a news report that the messenger RNA (mRNA)-based vaccine developer was researching vaccines designed to protect against hantaviruses. In a statement, Moderna disclosed that it has carried out early-stage vaccine research on hantaviruses with the U.S. Army Medical Research Institute of Infectious Diseases and is also partnering with the Vaccine Innovation Center at Korea University College of Medicine on a potential jab. “These efforts are early-stage and ongoing and reflect Moderna’s broader responsibility to develop countermeasures against emerging infectious diseases,” Moderna told Bloomberg News. As of Friday, the World Health Organization (WHO) has reported eight cases of hantavirus, including three deaths, among passengers aboard the MV Hondius cruise ship, traveling between Argentina and the Canary Islands in the Atlantic Ocean.
  • Viridian Therapeutics (NASDAQ: VRDN) shares jumped 33% from $14.06 to $18.75 Tuesday after the autoimmune and rare disease drug developer announced positive topline data from the Phase III REVEAL‑2 trial (NCT06625398) assessing elegrobart in chronic thyroid eye disease (TED). Doses of elegrobart given every 4 and 8 weeks achieved what Viridian called “highly statistically significant” 50% and 54% proptosis responder rates (PRR) at week 24, respectively, vs. 15% for placebo. Elegrobart is a subcutaneously delivered, half‑life‑extended monoclonal antibody targeting the insulin‑like growth factor‑1 receptor (IGF‑1R). Viridian said it remains on track to submit a Biologics License Application (BLA) to the FDA for elegrobart in Q1 2027. Viridian cashed in on the news by launching underwritten public offerings of $150 million in convertible senior notes due 2032 and $100 million in Series B nonvoting convertible preferred stock.

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Novelty Nobility Expands AGC Biologics Deal to Take Product Candidate Through GMP Manufacturing

Korea-based Novelty Nobility expanded its agreement with CDMO AGC Biologics to advance their bispecific antibody drug candidate through process development and GMP manufacturing at AGC Biologics’ facility in Chiba, Japan. The project leverages AGC Biologics’ global network, having completed cell line development in Copenhagen, Denmark, to be followed by tech transfer to the Chiba site for the next manufacturing stages.

“We believe this bispecific antibody has the potential to offer a truly differentiated treatment option for patients with neovascular retinal diseases,” said Sang Gyu Park, CEO of Novelty Nobility.

The product candidate, NN4101, a first-in-class, connects a fully human anti-c-Kit monoclonal antibody with a vascular endothelial growth factor (VEGF) trap.

“Our mammalian expression teams are adept at handling complex proteins, and we are a world leader in applying flexible, single-use bioreactor technology,” commented said Tadashi Murano, president of the AGC Life Science Company. “We are proud to support Novelty Nobility as they advance this innovative candidate toward the clinic.”

To further support growing demand in the region and globally, AGC is also expanding its facility in Yokohama, Japan, which is designed to utilize single-use bioreactor technology to offer large-scale GMP manufacturing.

 

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Cultural Relevance and Acceptability of Cognitive Behavioral Therapy Techniques Adapted by AI or a Human Psychologist: Experimental Study

Background: Evidence-based psychological interventions are usually not accessed by marginalized groups such as refugees. Culturally adapted psychological interventions have reported larger effect sizes than nonadapted psychological interventions. However, the cultural adaptation of interventions is a lengthy process, entailing a challenge. One potential solution to overcome this challenge is the use of artificial intelligence (AI). Objective: The aim of this study was to investigate and compare the perceived cultural relevance and acceptability of 2 common cognitive behavioral therapy (CBT) techniques when translated and culturally adapted by AI versus a human psychologist. Methods: In a 2×2 factorial design, the text generator type (AI vs human psychologist) and the CBT technique (cognitive restructuring vs behavior modification) were compared. CBT technique texts translated and culturally adapted either by AI or by a human psychologist were blindly rated using the Cultural Relevance Questionnaire and the Theoretical Framework of Acceptability. Raters were Arabic-speaking refugees and immigrants, aged between 18 and 69 years, residing in Sweden, Denmark, and Germany. Raters were randomly allocated to 1 of 4 conditions. Each condition consisted of 2 stimuli. Two-factor between-subject design analyses were used to analyze the data. Results: A significant main effect of the text generator domain type (=.02; η²=0.045) was found in the first rating, with texts adapted by the AI domain perceived as more culturally relevant than those adapted by the human domain. No significant main effect of the CBT technique was found in the first rating (=.10; η²=0.022). There were no differences in the second rating. Regarding acceptability, no significant main effects of text generator domain type (=.09; η²=0.024) or the CBT technique (=.88; η²=0.001) were found in either of the ratings. Conclusions: CBT technique materials adapted by AI may be perceived as similarly culturally relevant as those adapted by a human psychologist. This finding implies the potential to accelerate the cultural adaptation of psychological interventions. However, AI still needs to be used with caution and in accordance with rigorous safety standards and robust frameworks.
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Adaptive, Agent-Oriented Control for Biomanufacturing Systems

Agentic AI goes beyond predictive and generative AI and, in biomanufacturing, has the potential to enhance efficiency by integrating with existing manufacturing infrastructure such as IoT sensors, process information management systems, management execution systems, and even enterprise resource planning software. The challenge, however, is that industrial biomanufacturing processes are complex, demand resilience, and are tightly regulated.

The Adaptive Agent-Oriented System Control (AAOSC) framework developed by a team from the Technical University of Denmark (DTU) and SiC Systems addresses that challenge through a decentralized control layer. In it, “specialized autonomous agent ‘hives’ [are] coordinating digital twin enabled manufacturing infrastructure and real-time communications protocols.” The latter lets biomanufacturers integrate models, make learning-based inferences, and control process systems.

Four AAOSC case studies were discussed in a recent paper by Seyed Soheil Mansouri, PhD, professor at DTU and co-founder and CSO of SiC Systems and Christopher J. Savoie, PhD, co-founder and CEO of SiC Systems, and inventor of the agentic AI technology behind Siri. Those case studies “demonstrate AAOSO’s prowess [in] reducing deviating durations, averting shutdowns in severe fault scenarios, and boosting efficiency through virtual quantum and classical sensing and decentralized reasoning, all while aligning with regulatory imperatives…”

Despite its capabilities in monitoring process, identifying discrepancies, and recommending solutions, agentic AI “is not yet fully ready for complete, independent control in biopharmaceutical manufacturing,” Mansouri tells GEN. “Any AI that directly affects medicine quality still needs strong human oversight and full approval. We are getting closer, but full integration requires official [regulatory] clearance.”

The AAOSC framework that Mansouri and colleagues built may be unique in the industry. It isn’t all-knowing and “God-like,” he points out. Instead, “our methods are grounded in physics, chemistry, and biology within an agent ‘hive’—an orchestration of rule-based, mathematically informed agents. So, AAOSC is, foundationally, a different philosophy of building AI [in which] humans are in control.”

First, run in shadow mode

To introduce agentic AI, Mansouri advises starting gradually. “Run the AI alongside your current control systems in shadow mode—it watches everything and gives recommendations, but doesn’t make any actual changes without human oversight. This lets the teams learn how it works without any risks to production. Once confident, you can slowly expand its role while always keeping humans in final control.”

Both the FDA and EMA require systems that are fixed rather than continuously learning, he points out, and that can complicate adoption. To minimize the potential for regulatory issues that may arise by integrating AI into manufacturing processes, “work closely with your quality and regulatory teams from the beginning.

“Always maintain clear human responsibility, so no one is left wondering who is accountable if something goes wrong. Strong cybersecurity is essential,” Mansouri adds, “because these AI agents connect and talk to each other.” Therefore, “Start small, test thoroughly, and talk to regulators early.”

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