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< Back Metabolomics and Markers: Insights into Biological Ageing Study unveils a network of metabolic markers associated with rapid and healthy ageing. Assessing biological age, much more so than chronological age, holds immense significance for understanding healthspan and developing targeted interventions. Several studies have explored aging indicators using "omics" data and recent metabolomic analyses have offered novel insights into age-related diseases and longevity. However, many studies are limited in scope, either by the number of metabolites profiled or by their reliance on chronological age. One such study utilising this metabolomic approach to determining biological age was recently conducted by researchers at the University of Pittsburgh. Looking to distinguish chronological aging from biological age, this study, in a first for the field according to the authors, used a cohort that had a negative correlation between biological and chronological aging, thereby allowing for the isolation of metabolic changes that likely occur during biological aging. Remarkably, the study identified a panel of 25 metabolites, termed the HAM index, that robustly predicted healthy biological aging. Importantly, this predictive power remained unaffected by demographic and lifestyle factors such as gender, race, and smoking status. Among the key findings, acylcarnitines emerged as pivotal players in regulating lipid metabolism, with distinct patterns observed between rapid agers and healthy agers. Elevated levels of acylcarnitines associated with β-oxidation were characteristic of healthy agers, while rapid agers exhibited heightened levels of dicarboxylic fatty acids (DCAs), indicating increased ω-oxidation. The balance between these pathways may significantly influence biological age, with potential implications for healthspan and longevity. Further analysis revealed specific metabolites, such as eicosenoylcarnitine and β-cryptoxanthin, as potential markers of healthy aging. Eicosenoylcarnitine, in particular, demonstrated a strong discriminatory power between healthy and rapid agers, suggesting its potential as a biomarker for assessing biological age. Similarly, β-cryptoxanthin, a carotenoid found in fruits and vegetables, showed associations with reduced risk of age-related diseases, highlighting its role in promoting healthy aging. Additionally, the study shed light on the influence of gender on aging, with distinct metabolic signatures observed between male and female healthy agers. Notably, very long-chain acylcarnitines were elevated in female healthy agers, indicating active peroxisomal activity associated with increased longevity. Conversely, male healthy agers exhibited higher levels of degraded products of oxidized proteins, suggesting efficient degradation and removal of accumulated oxidative damage. Exploration of senescence-associated secretory phenotype (SASP) factors uncovered potential indicators of rapid biological aging, with elevated levels of CCL-2/MCP-1 and cystatin C observed in rapid agers. The strong association between these factors and age-related pathologies underscores their potential as biomarkers for assessing biological age. While the study offers valuable insights into biological aging, it also acknowledges certain limitations, including sample size constraints and potential confounding factors such as the intestinal microbiome and dietary influences. Future research endeavors will undoubtedly build upon these findings, expanding our understanding of the intricate mechanisms underlying aging and paving the way for targeted interventions to promote healthy aging. In conclusion, this study unveiled a distinct network of metabolites and inflammatory markers associated with rapid and healthy aging. Moving forward, leveraging this knowledge to develop multifaceted interventions targeting metabolic processes holds promise for enhancing the healthy lifespan of the aging population. Author BioFocus Newsroom Previous Next

Investor skepticism underscores challenges in demonstrating robust clinical value in psychedelic therapeutics for depression. < Back Compass Pathways' Phase 3 Psilocybin Readout Raises Efficacy Questions Despite Meeting Primary Endpoint Investor skepticism underscores challenges in demonstrating robust clinical value in psychedelic therapeutics for depression. In a long-anticipated clinical milestone for the psychedelics space, Compass Pathways reported topline results from a pivotal Phase 3 study of its proprietary psilocybin formulation, COMP360, in treatment-resistant depression (TRD). While the study met its primary endpoint, the magnitude of benefit and lack of detailed secondary outcomes left markets underwhelmed, sending shares tumbling by nearly 50% in early trading . The U.K.-based biotech enrolled 258 TRD patients, administering a single dose of COMP360 or placebo in a double-blind design, followed by psychological support. At six weeks, the psilocybin arm demonstrated a statistically significant 3.6-point reduction on the MADRS scale relative to placebo, a result Compass positioned as both clinically meaningful and a validation of its development approach. However, in an environment of growing competition and increasing investor scrutiny, the response was tepid. Analysts and key opinion leaders flagged the relatively modest separation from placebo, particularly in contrast to earlier Phase 2 data showing approximately a 6-point difference, and noted the absence of crucial secondary metrics such as remission and response rates. RBC Capital Markets analyst Leonid Timashev noted that in the absence of durability data or functional endpoints, a 3.6-point delta on MADRS may not be enough to drive investor confidence or payer differentiation. Futhermore, clinicians in their outreach indicated that a 4-point margin would be a minimum threshold of interest, with 5 points or more seen as indicative of a compelling treatment effect. This tempered enthusiasm may also reflect expectations shaped by recent competitors. GH Research, for example, reported promising results in an 81-patient trial of inhaled mebufotenin, a psilocybin analogue, showing nearly a 16-point placebo-adjusted reduction on the same scale at day eight. While direct comparisons are fraught due to protocol and timing differences, the contrast points towards a key challenge for Compass: demonstrating that COMP360 offers both efficacy and convenience superior to current alternatives. GH’s trial employed a titrated dose and evaluated outcomes at an earlier timepoint, which may have limited placebo response and enhanced effect size. These nuances matter, particularly in psychiatric trials where expectation effects are notoriously difficult to control. From a safety perspective, Compass reported no new signals, with its independent data monitoring committee confirming a consistent safety profile and no clinically meaningful imbalance in suicidality between treatment arms, a critical consideration in TRD populations. Still, commercial viability remains an open question. Johnson & Johnson’s Spravato ( esketamine ), an intranasal therapy for TRD approved in 2019, generated over $1 billion in sales last year, largely driven by a broader label and entrenched payer relationships. Compass, by contrast, is navigating an uncharted reimbursement landscape for psychedelic-assisted therapy, with questions remaining around scalability, infrastructure requirements, and healthcare provider training. Evercore ISI analyst Gavin Clark-Gartner downgraded the stock following the announcement, characterizing the outcome as insufficiently convincing. " With clinical and commercial question marks, the second [Phase 3 study] will remain a ‘show me’ story for investors in an increasingly competitive landscape,” he wrote. Those results, evaluating longer-term outcomes over a 26-week horizon, are expected in the second half of next year. Until then, Compass must contend not only with a skeptical market but with a rapidly evolving field that continues to challenge traditional notions of drug development in mental health. Author BioFocus Newsroom Previous Next

New clinical data at VIVA 2024 highlights intravascular lithotripsy as a breakthrough treatment for calcified lower limb lesions in peripheral artery disease. < Back Shockwave Medical Demonstrates Intravascular Lithotripsy's Efficacy for Lower Limb Lesions at VIVA 2024 New clinical data at VIVA 2024 highlights intravascular lithotripsy as a breakthrough treatment for calcified lower limb lesions in peripheral artery disease. Shockwave Medical , a leader in the development of intravascular lithotripsy (IVL) technologies, has presented new clinical data supporting the effectiveness of IVL in treating lower limb arterial lesions. The findings, shared in a late-breaking presentation at the VIVA 2024 conference, underscore the potential of Shockwave's IVL technology as a transformative treatment option for patients with peripheral artery disease (PAD). The late-breaking presentation at the Vascular Interventional Advances (VIVA) conference highlighted positive outcomes from the use of IVL in addressing calcified lesions in the lower limbs. Calcified lesions are notoriously difficult to treat with traditional methods, and the new data reinforces the growing evidence that IVL, which uses soundwave energy to break down arterial plaque, can offer significant advantages in improving vessel compliance and restoring blood flow. Dr. Jeffrey L. Ballard, an investigator involved in the study, emphasized that the results demonstrate the utility of Shockwave's IVL technology in addressing challenging lower limb lesions, which are often associated with PAD, a condition that affects millions of individuals worldwide. IVL’s ability to safely and effectively treat these calcified lesions marks a significant advancement in PAD management, offering patients a potential solution to a previously difficult-to-treat condition. The latest study results also indicate that IVL is not only safe but also effective in improving procedural success rates, enhancing post-procedure outcomes, and reducing the need for repeat interventions. These findings align with prior research that has demonstrated the effectiveness of Shockwave’s technology in treating coronary artery disease and now further validate its broader applicability in peripheral vascular disease. The VIVA 2024 presentation also emphasized the ongoing role of Shockwave Medical in advancing medical technology for PAD patients. By focusing on non-invasive solutions like IVL, the company is leading efforts to improve clinical outcomes and enhance the quality of life for those affected by vascular diseases. In conclusion, the newly presented data at VIVA 2024 further cements Shockwave Medical’s position as a pioneer in the field of vascular interventions, providing new hope for patients with calcified arterial lesions, particularly in the lower limbs. As the prevalence of PAD continues to rise globally, innovations such as IVL are set to play an increasingly vital role in managing this debilitating disease. Author BioFocus Newsroom Previous Next

In a phase 1 study, 81% of patients responded to IL18-boosted therapy, with over half achieving complete remission. < Back Breakthrough "Armoured" CAR T-Cell Therapy Shows Promising Results in Tough-to-Treat Lymphomas In a phase 1 study, 81% of patients responded to IL18-boosted therapy, with over half achieving complete remission. CAR T-cell therapy revolutionized cancer treatment by using a patient’s own immune cells to target blood cancers. However, its impact has been limited by relapse and resistance , especially in B-cell lymphomas—where more than half of patients do not achieve lasting remission after receiving current FDA-approved therapies. Researchers at Penn Medicine have developed a new, next-generation version of this therapy, called huCART19-IL18, designed to overcome these challenges. Unlike traditional CAR T cells, this “armoured” version not only targets cancer cells but also secretes interleukin-18 (IL18), a molecule that enhances immune activity and supports the engineered cells within the tumor microenvironment. In a recently published phase 1 study in the New England Journal of Medicine , the results were highly encouraging. Among 21 patients with aggressive, treatment-resistant B-cell lymphomas, most of whom had received multiple prior therapies, including earlier-generation CAR T products, 81% experienced tumor shrinkage, and 52% achieved complete remission. Some patients have remained in remission for over two years, suggesting durable responses may be possible with this approach. Importantly, the therapy did not introduce new or unexpected safety issues. Side effects such as cytokine release syndrome and neurotoxicity remained consistent with those observed in standard CAR T therapies and were manageable using existing treatment protocols. The strategy behind huCART19-IL18 centers on boosting the immune system’s ability to sustain its attack on cancer cells. Like most other CAR T therapies for B-cell lymphoma, the engineered T cells are designed to recognize the CD19 protein found on malignant cells. What sets this therapy apart is its built-in production of IL18, a pro-inflammatory cytokine that helps activate and recruit other immune cells, reinforcing the overall immune response. This addition appears to counteract common barriers to CAR T-cell effectiveness, such as immune suppression within the tumor environment and T-cell exhaustion. Early biological data collected during the study supports the idea that IL18 significantly contributed to the high response rates observed. One of the other major innovations of the Penn team is a streamlined manufacturing process that reduces production time for the CAR T cells from the standard 9–14 days down to just three. For patients with fast-growing cancers, this shorter turnaround can make a critical difference, allowing treatment to begin before the disease progresses further. There’s also evidence that this quicker manufacturing timeline may improve the therapeutic potency of the T cells. This study marks the first time a cytokine-enhanced CAR T-cell therapy has been tested in patients with blood cancer, and the implications extend well beyond lymphoma. The underlying concept, arming CAR T cells with immune-boosting cytokines, could be applied to other cancers, including those where CAR T therapies have historically shown limited success, such as solid tumors. Building on these results, the researchers are preparing additional clinical trials, including studies targeting acute lymphoblastic leukemia and chronic lymphocytic leukemia. A trial for non-Hodgkin’s lymphoma using a similar IL18-enhanced CAR T product is already underway. Efforts are also ongoing to refine and scale the manufacturing process in partnership with a biotechnology spinout, with the goal of expanding access to these advanced therapies. Beyond clinical outcomes, the data generated from this trial is providing valuable insight into how and why CAR T therapies fail in some cases, helping guide future improvements in treatment design and patient selection. This therapy represents a significant step forward in the evolution of personalized cancer immunotherapy, offering new hope for patients with few remaining options, and potentially laying the groundwork for broader applications in oncology. Author BioFocus Newsroom Previous Next

Jiangnan University scientists takes a look at how artificial intelligence may transform the bioprocessing industry. < Back Artificial Intelligence in Bioprocess Control and Optimization Jiangnan University scientists takes a look at how artificial intelligence may transform the bioprocessing industry. Industrial bioprocesses play a crucial role in producing biofuels, materials, and healthcare products. However, challenges such as low bioconversion rates and productivity limitations persist. The transfer from lab to industrial scale, known as the "scale-up effect," introduces additional complexities. Over the past decades, strides have been made in optimizing bioprocesses, utilizing techniques like orthogonal experimental design (OED) and response surface methodology (RSM). Despite these advancements, there is a growing need for more sophisticated control and optimization methods. In this context, artificial intelligence (AI) has emerged as a promising solution, offering data-driven approaches independent of complex mathematical models. A review authored by members of Jiangnan University, China, published in February 2023, looks at how AI can revolutionise the bioprocess industry, and offers theoretical guidance on how to incorporate AI into bioprocess optimization. AI-Guided Modeling and Optimization of Bioprocess To address the intricate nature of bioprocesses, AI-guided modeling approaches have gained prominence. These approaches, whether theory-driven or data-driven, provide insights into critical process parameters (CPPs). Classical methods like OED and RSM have been effective, but AI introduces new dimensions such as machine learning algorithms, where artificial neural networks (ANN) or particle swarm optimization (PSO), can be applied to model and optimize various bioprocesses. These technologies offer a more nuanced understanding of the nonlinear relationships between variables. Rapid Detection Based on Spectroscopy and Image Recent advancements in spectroscopy, particularly near-infrared reflectance spectroscopy (NIRS), have enabled rapid detection in bioprocesses. Spectroscopy proves convenient and accurate, utilizing overtones and combination bands of functional groups for qualitative and quantitative analysis. Image recognition technology further aids in the swift assessment of compost maturity, showcasing the potential of AI-assisted rapid detection and monitoring technologies. AI-Guided Bioprocess Control Effective control strategies are essential for optimizing the yield and productivity of bioprocesses. Unlike chemical processes, bioprocesses exhibit high time scale variability due to factors like inoculation size, seed age, and culture conditions. AI technologies, such as machine vision and soft sensors, have been instrumental in developing smart control strategies that adapt to these dynamic conditions, enhancing the precision of bioprocess control. Challenges and Perspectives While AI technologies offer significant promise in bioprocess optimization and control, challenges and research gaps certainly exist. Obtaining relevant data remains a crucial hurdle, demanding effective strategies for data acquisition. Additionally, there is a need for more comprehensive industrial applications of advanced control strategies, like adaptive control and model-based control. The authors suggest that addressing these challenges will be pivotal in realizing the full potential of AI in bioprocess optimization and control. In the review, the Jiangnan University author’s indicate the transformative role AI will likely have in advancing bioprocess control and optimization. Technologies such as ANN, SVM, FL, GA, and PSO have, and continue to, mature, offering valuable insights and improvements. The integration of machine vision, spectroscopy, and soft sensors enhances monitoring accuracy, while smart control strategies adapt to the dynamic nature of bioprocesses. As the bio-based economy continues to evolve, the judicious application of AI technologies holds immense promise for unlocking the full metabolic potential of microorganisms in industrial bioprocesses. Author BioFocus Newsroom Previous Next

First advanced solid tumour patient dosed in a phase I clinical trial assessing preliminary efficacy of bispecific antibody, NWY001. < Back Chipscreen NewWay Biosciences Initiates Phase I Clinical Trial First advanced solid tumour patient dosed in a phase I clinical trial assessing preliminary efficacy of bispecific antibody, NWY001. Chengdu Chipscreen NewWay Biosciences Co., Ltd. (NewWay) has marked a significant milestone with the initiation of the phase I clinical trial for NWY001, the world's first PD-1/CD40 bispecific antibody to enter clinical trials. The dosing of the first patient occurred on January 5, 2024, at Sun Yat-Sen University Cancer Center in China. NWY001 aims to transform "cold" tumors into "hot" tumors, potentially enhancing cancer patients' sensitivity to PD-(L)1 immune checkpoint inhibitors, particularly those resistant to PD-(L)1 antibody monotherapy. NWY001's unique mechanism involves the synergistic targeting of PD-1 and CD40 pathways, activating the CD40 pathway in a PD-1 dependent manner. This approach is designed to mitigate the common toxicities associated with CD40 agonistic monoclonal antibodies. The phase I clinical trial is a multi-center, non-randomized, open-label study focusing on evaluating safety, tolerability, preliminary efficacy, pharmacokinetic properties, and potential biomarkers associated with NWY001 treatment in patients with advanced solid tumors. Dr. Bin Liu, Scientific Director of Chipscreen NewWay, expressed gratitude to Sun Yat-Sen University Cancer Center, Chipscreen's clinical and related teams, and the enrolled patients and their families. The initiation of the trial is expected to address the ineffectiveness or toxicity challenges posed by PD-(L)1 immune checkpoint inhibitor monotherapy and combination therapies involving CD40 agonists. In a related development, on February 27th, 2023, Biocytogen Pharmaceuticals' subsidiary, Eucure (Beijing) Biopharma Co., Ltd., entered an exclusive licensing agreement with Chipscreen NewWay Biosciences for the clinical development and commercialization of bispecific antibody YH008 (NWY001) in Greater China, encompassing Mainland China, Hong Kong, Macau, and Taiwan. Chipscreen NewWay, a biotech company affiliated with Chipscreen, is dedicated to developing large molecules and novel therapeutic modalities, with a focus on oncology and autoimmunity. The company has built an extensive molecular R&D center in Chengdu Hi-Tech Zone, employing an experienced team for antibody and ADC R&D projects. Chipscreen, established in 2001, is a biopharmaceutical company specializing in original drug development across various disease areas, including oncology, metabolic diseases, autoimmune diseases, central nervous system disorders, and antiviral therapies. As the world eagerly awaits the results of the NWY001 phase I clinical trial, this groundbreaking PD-1/CD40 bispecific antibody represents a promising advancement in cancer treatment, offering hope for enhanced therapeutic outcomes in patients with advanced solid tumors. Author BioFocus Newsroom Previous Next

< Back NHS Delivers First CAR-T Treatment for Adult B-cell ALL Patient Pioneering ‘living drug’ offers new hope for adults with aggressive leukaemia. The first patient to receive a pioneering form of CAR-T therapy for aggressive leukaemia on the NHS has described the experience as both “fantastic” and “very sci-fi”. Oscar Murphy, 28, from Bury, became the inaugural recipient of the treatment for B-cell acute lymphoblastic leukaemia (B-cell ALL) at Manchester Royal Infirmary on 2 January, when he began the first of two infusions of his genetically modified immune cells. The immunotherapy, often referred to as a “living drug”, is designed to recognise and kill cancerous cells and will now be funded across several NHS centres in England. Around 50 patients a year are expected to qualify, though clinicians believe the number could rise. Murphy was diagnosed with B-cell ALL in March 2025 and initially underwent chemotherapy followed by a donor stem cell transplant in July. His cancer relapsed just months later. “The leukaemia I've got is so fast-acting,” he said. “It needs an even quicker response to stop it. And we've now got an answer for that.” Clinical trial data underpinning the NHS rollout showed 77% of patients entered remission after treatment, with half displaying no detectable cancer three and a half years later. On average, patients gained an additional 15.6 months of life. According to Murphy’s haematologist, Dr Eleni Tholouli, the new iteration of CAR-T therapy is both safer and more effective than existing options. “Usually, this type of leukaemia is very aggressive and adult patients don't live beyond six to eight months. With this therapy, we are able to offer them years and potentially a cure. It's very significant and is revolutionising the way we tackle this cancer.” CAR-T therapy has been available on the NHS for several years for certain leukaemias and lymphomas, but this marks the first time adults with B-cell ALL have had access to the treatment. The breakthrough also comes amid ongoing conversations about who can access CAR-T therapies and when. In our earlier feature on Myeloma UK’s campaigning efforts, stakeholders warned that while the science is advancing quickly, equitable access across the NHS is yet to catch up. Murphy’s personalised therapy required T-cells to be extracted and sent to a manufacturing site in Stevenage, where they were engineered using a viral vector to introduce a genetic sequence that enables them to recognise malignant cells. Newly expressed surface receptors act like a lock-and-key system to identify the cancer, transforming the cells into chimeric antigen receptor T-cells, or CAR-T cells, which are expanded into the millions before being cryopreserved. The first infusion delivered around 100 million CAR-T cells contained in just a few teaspoons of fluid. A second infusion of 300 million cells followed. As a living therapy, the reprogrammed T-cells are expected to persist in the body, continue dividing and maintain anti-cancer activity over time. Murphy admitted he was astonished that such a small volume could deliver such a potent intervention. “It's very sci-fi, but if it means it gets rid of the cancer permanently and my own cells can do it it's just fantastic.” The treatment is manufactured by Autolus , a University College London spin-out . During earlier clinical studies, patient cells had to be shipped to laboratories in the US, underscoring the significance of onshore manufacturing capacity. The therapy carries a list price of £372,000 per infusion, though the NHS has negotiated confidential discounts. Eligible patients over 26 whose B-cell ALL has relapsed or failed to respond to treatment will be able to access the therapy at centres in Manchester, Cambridge, Newcastle, Sheffield, Plymouth and London. Patients from Wales and Northern Ireland will need to travel to England, and the treatment is not yet approved in Scotland. NHS England estimates that around 50 patients a year may benefit, but Tholouli told the BBC she believed more candidates will emerge, and predicted the therapy could ultimately replace stem cell transplantation as a first-line approach. Prof Peter Johnson, NHS National Clinical Director for Cancer, described the development as a “landmark moment” for people with aggressive blood cancers, adding that it was “remarkable” that a treatment conceived through UK research was now being delivered across the health service. “It will help more people like Oscar live longer and healthier lives.” The potential of the therapy is already evident in earlier patients. Chris Williams, 29, from Belfast, who was treated in Manchester while the therapy was still experimental, has now been in remission for nearly three years. “A few years ago I was very unwell and now I'm able to live a full life. I was able to go back to work. I also met Chloe and now we're engaged. I have fantastic support from my family and they are over the moon.” Murphy married his fiancée Lauren at Manchester Royal Infirmary last month, conscious of the uncertainties surrounding his condition, though the couple have planned a second ceremony for October. Looking ahead, his ambitions are disarmingly ordinary. “I want children and the white picket fence with my amazing wife, I just want that normality. This is my gateway to doing it and I can't wait.” Author BioFocus Newsroom Previous Next

< Back Body Clock Protein Found to Protect the Brain by Boosting Vital Energy Molecule Circadian regulator REV-ERBα emerges as a brain-specific controller of NAD+ and tau pathology. A new study has uncovered a surprising, brain-specific mechanism through which the circadian protein REV-ERBα regulates levels of the key metabolic cofactor NAD+, revealing a potential new therapeutic target for Alzheimer’s disease (AD) and related neurodegenerative disorders. Researchers report that REV-ERBα suppresses brain NAD+ levels by promoting expression of the NAD+-consuming enzyme CD38, a mechanism distinct from its previously described role in the heart. In the brain, deleting or inhibiting REV-ERBα increased NAD+ concentrations, improved astrocyte function, and reduced tau accumulation and neurodegeneration in mouse models of tauopathy. The findings, published this week in Nature Neuroscience, redefine how NAD+ metabolism is regulated in the central nervous system and highlight the therapeutic potential of REV-ERBα inhibitors and CD38 blockers for neurodegenerative diseases. Nicotinamide adenine dinucleotide (NAD+) is an essential metabolic cofactor involved in redox balance, DNA repair, and sirtuin-dependent protein deacetylation. Declining NAD+ levels are a hallmark of aging and have been linked to neurodegeneration. While boosting NAD+ has been proposed as a neuroprotective strategy, the molecular control of NAD+ in the brain has remained unclear. REV-ERBα, a nuclear receptor that integrates circadian rhythms with metabolic and inflammatory pathways, was already known to regulate NAD+ in the heart by controlling NAMPT, the rate-limiting enzyme in NAD+ synthesis. In this new work, however, the authors demonstrate that brain REV-ERBα does not affect NAMPT. Instead, it operates through a distinct astrocyte-specific mechanism, repressing the transcription factor NFIL3, which in turn suppresses CD38, the enzyme responsible for NAD+ consumption. Deletion of REV-ERBα, either globally or specifically in astrocytes, increased NAD+ levels in the brain and protected against tau pathology in P301S tauopathy mice, a model of Alzheimer’s disease. Pharmacological inhibition of REV-ERBα with the antagonist SR8278 produced similar neuroprotective effects. Mechanistic studies revealed that elevated NAD+ in astrocytes enhanced lysosomal activity and tau uptake, promoting clearance of toxic tau aggregates. This astrocyte-driven protection occurred without detectable neuroinflammation, suggesting that targeted modulation of REV-ERBα can support protein homeostasis in the aging brain. The data also contrast with previous findings that microglia-specific REV-ERBα deletion worsens tau pathology in male mice, highlighting cell-type- and tissue-specific roles for this nuclear receptor. Overall, the balance of effects, particularly in astrocytes, appears protective when REV-ERBα activity is inhibited. The discovery of a REV-ERBα–NFIL3–CD38 axis that governs NAD+ metabolism in the brain opens multiple translational avenues. REV-ERBα antagonists may provide a means to boost brain NAD+ and mitigate tau accumulation. CD38 inhibitors, already under investigation for metabolic and inflammatory disorders, could gain traction as candidates for neurodegenerative disease modification. The work underscores the importance of cell-type-selective targeting in drug development for circadian and metabolic regulators. The researchers note that while total genetic deletion of REV-ERBα can have deleterious effects during development, partial pharmacological inhibition in adulthood appears to enhance neuroprotection without adverse inflammation. This nuance could guide the design of small-molecule modulators optimized for CNS indications. REV-ERBα’s role in linking circadian regulation, metabolism, and proteostasis positions it as a key node in the biology of aging and neurodegeneration. As lead author notes, “Our results reveal that REV-ERBα functions very differently across tissues, suppressing NAD+ production in the heart, but restraining NAD+ consumption in the brain. Understanding these tissue-specific mechanisms is essential for translating circadian biology into safe, effective therapeutics.” Given the ongoing industrial interest in NAD+ augmentation, circadian modulation, and glial biology, this study provides both mechanistic clarity and new targets for drug discovery programs aimed at Alzheimer’s disease, tauopathies, and age-related brain decline. Author BioFocus Newsroom Previous Next

New US study evaluates the cost-effectiveness of semaglutide in treating non-diabetic patients with obesity and cardiovascular disease. < Back Weighing the Cost of Semaglutide New US study evaluates the cost-effectiveness of semaglutide in treating non-diabetic patients with obesity and cardiovascular disease. It is a widely held truth that obesity is more than just a health crisis, it is an economic burden. Due to the range of comorbidities that all too often accompany obesity, the healthcare costs associated with obesity are extensive, and with rates of obesity continuing to increase, particularly in the U.S , where nearly half of adults are projected to be obese by 2030, there is a critical need for efficacious interventions. There are many factors that contribute to higher rates of obesity - wealth inequality, genetics, culture, sleep, to name but a few, and these all need to be factored into addressing a wider strategic goal of reducing obesity. At the moment though, at least in the US, the pharmaceutical industry is focused squarely on weight loss medication, specifically GLP-1 receptor agonists. Originally discovered to treat diabetes, these molecules, semaglutide being the most well known, help reduce weight loss by suppressing appetite and slowing digestion, making patients feel fuller for longer and meaning that in conjunction with a diet and exercise regime, patients can successfully lower their calorie intake and lose weight. Semaglutide is the active ingredient in Novo Nordisk’s blockbuster Wegovy anti-obesity medication, which alongside weight loss of ~17%, has also been shown to significantly reduce the risk of cardiovascular disease. Novo Nordisk has been questioned about the price of Wegovy in the U.S, where a month-long supply of Wegovy® costs 5x more than the second most expensive list price in Japan ($939 vs $169). In September of last year, Novo’s CEO Lars Fruergaard Jørgensen was grilled by Bernie Sanders on the price differences. Well-documented access issues due to manufacturing difficulties causing supply-driven price increases were of course mentioned (although this has recently changed with the FDA taking Wegovy off the shortage list ) but, predictably, the injustices in the difference in prices were attributed to the injustices in the U.S. health system and the market dynamics that underpin the system. So with the medical zeitgeist dominated by GLP-1 receptor agonists and their undeniably impressive efficacy in treating weight loss and diabetes, let’s look at the new study published in the Journal of Medical Economics, which investigated whether semaglutide (2.4 mg) represents a cost-effective solution for non-diabetic people with obesity and cardiovascular disease. This US-based research builds on the landmark SELECT trial, which showed that semaglutide reduced the risk of major cardiovascular events like heart attacks and strokes by 20%. The study used a Markov-state cost-effectiveness model using trial-derived data to simulate 100,000 individuals with obesity and established cardiovascular disease. It compared two groups: those who received semaglutide alongside standard of care (SoC) - an approved exercise and diet regime - and those who received SoC alone. The researchers then assessed lifetime treatment costs, savings from avoided medical complications, and overall improvements in quality of life. It was found that over a modelled lifetime horizon, semaglutide prevented an estimated 2,791 non-fatal heart attacks, 3,000 coronary revascularizations, and 487 strokes per 100,000 treated individuals. The treatment also lowered the likelihood of developing type 2 diabetes by 6.53 percentage points over 20 years. Although the drug itself costs an average of $47,353 per patient over their lifetime, it offsets expenses related to diabetes, kidney disease, and cardiovascular events, leading to an incremental cost of $29,767 per patient. Patients on semaglutide gained an average of 0.218 additional quality-adjusted life years (QALYs), a key metric in health economics. Cost-effectiveness in healthcare is often measured by the incremental cost-effectiveness ratio (ICER), which is the cost per QALY gained. At its list price, semaglutide’s ICER came in at $136,271 per QALY, which falls within the ‘intermediate value’ range set by the American College of Cardiology and American Heart Association . However, when applying the estimated average manufacturer discount (48%), which aligns with real-world pricing strategies, the ICER dropped to just $32,219 per QALY, making it a ‘high-value intervention.’ While the numbers are promising, the study does acknowledge certain limitations. The trial population may not fully represent the broader U.S. demographic, and the long-term effects of weight regain after discontinuing semaglutide remain uncertain. However, the findings suggest that with proper pricing strategies, semaglutide could offer a cost-effective solution for a population at high cardiovascular risk. Given the increasing recognition of obesity as a chronic disease rather than a lifestyle issue, semaglutide’s dual benefits, weight loss and cardiovascular protection, could push insurers and policymakers to rethink coverage and access. As healthcare systems grapple with the financial toll of obesity-related diseases, the case for semaglutide as a cost-effective intervention is growing stronger by the day. The obesity medication market is becoming increasingly saturated. Currently, Novo’s closest competitor is Eli Lilly, with their tirzepatide GIP/GLP-1 dual agonist (marketed as Mounjaro for diabetes and Zepbound for obesity) showing slightly better weight loss than semaglutide. There is a fierce race to push the boundaries of obtainable weight loss, of different methods of administration (oral solutions are in the pipeline so patients don’t have to use a pen), of indications for comorbidities, of actually being able to generate enough supply to meet demand. With pharma continually pushing the limits of weight loss, it begs the question: how much weight loss is too much weight loss? Clinicians and patients are fearing that there may come a point where the weight loss is so excessive that it could actually create a host of health issues. That said, what is clear is that these anti obesity drugs are incredibly powerful, and, in the case of semaglutide, represent a cost-effective obesity treatment. Author BioFocus Newsroom Previous Next

UK start-up's new platform promises to cut GLP-1 discontinuation rates by tailoring dose escalation to each patient's response. < Back Closed Loop Medicine Brings Personalised GLP-1 Dosing to the U.S with WeDosify UK start-up's new platform promises to cut GLP-1 discontinuation rates by tailoring dose escalation to each patient's response. Closed Loop Medicine Ltd (CLM), a UK-based leader in personalised pharmaceutical dosing, has announced the U.S. launch of WeDosify, its first commercially available product. The platform is designed to help clinicians improve long-term adherence to GLP-1 therapies by tailoring dose escalation and maintenance to each patient’s tolerability and treatment goals. Global demand for anti-obesity medicines continues to accelerate, with the market expected to grow from US$30 billion in 2024 to US$100 billion by 2030. Yet, despite their efficacy, up to 44% of patients stop GLP-1 therapy within six months, a figure that rises to 60% within a year, largely because of dose-related gastrointestinal side effects such as nausea and diarrhoea, as well as a lack of structured support for long-term use. WeDosify aims to address this problem by presenting data-driven, individualised dosing options for clinical review, updating recommendations in real time as a patient responds to treatment. The technology is informed by 29 studies and more than 15,000 patient profiles, underpinned by pharmacokinetic/pharmacodynamic modelling. A recent survey found that 91% of GLP-1 patients would be more likely to stay on treatment if supported by WeDosify. One respondent explained: “Having data helps you make personalized decisions and makes you more engaged with your weight loss journey.” Clinicians are already adopting the tool. Dr. Neese, from Amarillo Premier Research in Texas, commented: “I am delighted to have the opportunity to share WeDosify with my patients. It will enable me to work with each patient to determine a course of action that is genuinely personal to them, helping them to achieve lasting weight loss.” Kate Woolland, CEO of CLM, positioned the launch as a milestone: “WeDosify is the first product that offers genuinely personalized recommendations which update in real time to reflect how the patient is responding to the drug. For the first time, patients can see what their weight loss journey might look like and work alongside their clinician to make decisions about their health. This is a genuine gamechanger.” The timing is significant. Regulatory efforts such as the Right Drug Dose Now Act and the White House’s HTI-4 digital health commitment highlight growing emphasis on precision prescribing and reducing adverse drug events. Meanwhile, drug developers are increasingly focused on balancing GLP-1 efficacy with tolerability; slow, individualised titration schedules have been shown to improve patient outcomes in recent clinical studies. By tackling adherence, CLM hopes WeDosify will extend the undoubted benefits of GLP-1 therapy to more patients for longer, potentially setting a new standard for how weight-loss medicines are used in practice. Author BioFocus Newsroom Previous Next

We discuss the significance of small molecule drugs in oncology, the rise of China’s biotech industry, and the potential market impact of this collaboration. < Back Novartis Pays China’s Baiyu $70M Upfront, with $1.1B in Potential Milestones for Small Molecule Cancer Candidate We discuss the significance of small molecule drugs in oncology, the rise of China’s biotech industry, and the potential market impact of this collaboration. In a bold effort to expand its oncology pipeline, Swiss pharmaceutical giant Novartis has entered into a licensing agreement with China’s Chengdu Baiyu Pharmaceutical . This partnership focuses on the development of a promising small molecule cancer candidate, with Novartis paying an initial $70 million upfront and committing to milestone payments of up to $1.1 billion based on clinical, regulatory, and commercial achievements. This deal reflects the increasing importance of targeted therapies in cancer treatment and the growing global significance of China’s biotech industry. It also highlights Novartis’s strategy of augmenting its oncology portfolio with cutting-edge treatments developed through partnerships, particularly in the lucrative and competitive field of cancer therapy. The Deal Structure and Strategic Importance The deal, announced in October 2024, grants Novartis exclusive global rights, excluding China, to Baiyu’s small molecule cancer candidate. The upfront payment of $70 million is a significant show of confidence in Baiyu's research and development capabilities. The potential $1.1 billion in additional payments underscores the high stakes involved in oncology drug development, where the financial and scientific risks are substantial but the rewards, in terms of market share and patient impact, can be immense. Small molecule drugs, which are chemically synthesized and can enter cells easily due to their size, are a key area of focus in cancer treatment. Unlike biologics, which target specific proteins on the surface of cancer cells, small molecules can interfere with the internal mechanisms of these cells, often targeting kinases or other intracellular proteins essential for cancer progression. Baiyu's candidate is aimed at a specific molecular target that is believed to play a critical role in the growth and survival of certain cancers, though specific details about the drug’s mechanism have not been widely disclosed. For Novartis, this collaboration marks a continuation of its efforts to reinforce its position as a leader in oncology. The company has been a pioneer in cancer treatments, notably with groundbreaking drugs such as Gleevec (imatinib) for chronic myeloid leukemia and CAR-T therapies for blood cancers. Adding Baiyu's small molecule candidate to its pipeline is consistent with Novartis’s focus on next-generation cancer therapies that are more targeted, effective, and tailored to individual patient needs. China's Rising Biotech Industry The partnership also illustrates the growing influence of China's biotech sector on the global pharmaceutical landscape. Historically, China’s pharmaceutical industry focused primarily on generics, but over the past decade, the country has made significant strides in developing innovative therapies. Baiyu Biotechnology, a relatively young player in China’s biotech scene, has emerged as a leader in precision oncology, leveraging its expertise in medicinal chemistry and translational research to develop first-in-class or best-in-class small molecules aimed at cancer. The deal with Novartis not only brings international validation to Baiyu’s work but also reflects the broader trend of global pharmaceutical companies seeking partnerships with Chinese biotechs. China’s government has implemented various policies to foster innovation in the biotech sector, offering incentives for research and development, enhancing intellectual property protections, and fast-tracking regulatory approvals for breakthrough therapies. As a result, Chinese biotechs are becoming more competitive in the global market, attracting attention from pharmaceutical giants seeking new drugs and technologies. Potential Market Impact and Future Outlook The potential $1.1 billion in milestone payments suggests that Novartis views this small molecule candidate as a potential blockbuster, with significant commercial potential if it can successfully navigate clinical trials and gain regulatory approval. The oncology market remains one of the most lucrative areas in pharmaceuticals, driven by rising cancer prevalence, increasing demand for more effective treatments, and advances in precision medicine. If Baiyu’s candidate proves successful, it could join a growing list of small molecule cancer therapies that have achieved blockbuster status. Small molecules, while traditionally overshadowed by biologics in recent years, have seen a resurgence in oncology due to their versatility and the development of novel mechanisms of action. Unlike large biologics, small molecules can be administered orally, making them more convenient for patients and potentially improving adherence to treatment regimens. The deal also has strategic value for both companies beyond the immediate financials. For Novartis, partnering with Baiyu allows the company to expand its footprint in Asia, a rapidly growing market for cancer therapies. It also provides access to Baiyu’s cutting-edge research in medicinal chemistry, potentially opening the door for future collaborations. For Baiyu, the partnership offers significant financial resources to advance its research, as well as the opportunity to leverage Novartis’s global regulatory, manufacturing, and commercial expertise to bring its candidate to market outside of China. The Novartis–Baiyu partnership is a prime example of the increasingly global nature of drug development, where innovation often arises from collaborations that span continents. For Novartis, this deal enhances its already robust oncology portfolio, allowing it to continue delivering cutting-edge therapies to cancer patients worldwide. For Baiyu, the collaboration with a pharmaceutical giant like Novartis represents an important milestone in its development as a leading player in China’s rapidly advancing biotech industry. Cancer continues to be a leading cause of death worldwide. 2022 saw just shy of 20 million new cases worldwide, with this number expected to increase to 29.9 million by 2040 equating to 15.3 million deaths. As such, breakthroughs in targeted therapies, such as Baiyu's small molecule candidate, offer hope for more effective and personalized treatments. The financial and scientific investment from Novartis underscores the potential of this candidate, and the broader partnership demonstrates how global pharmaceutical companies are increasingly looking to China for innovative solutions in one of the most critical areas of medicine. Author BioFocus Newsroom Previous Next

Darmiyan receives FDA approval for BrainSee, the first prognostic test for predicting likelihood of progression to Alzheimer's dementia. < Back FDA Approves the First Prognostic Test for Alzheimer’s Progression Darmiyan receives FDA approval for BrainSee, the first prognostic test for predicting likelihood of progression to Alzheimer's dementia. Darmiyan, Inc., a leader in brain health innovation, announces a groundbreaking achievement: FDA's De Novo approval of BrainSee, the world's first prognostic test for predicting the likelihood of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's dementia. This approval is a significant leap forward in Alzheimer's diagnostics, showcasing the potential for proactive brain health management on a global scale. BrainSee is the clinical application of Darmiyan's patented core proprietary technology. It leverages over 40 years of cutting-edge brain science, incorporating advanced whole-brain image analysis and medical artificial intelligence (AI). It is a highly-scalable and fully-automated software platform that utilizes standard clinical brain MRI and cognitive assessments to generate an objective score predicting the likelihood of progression to Alzheimer's dementia within five years. Over 10 million Americans and more than 100 million global patients face aMCI, meaning BrainSee addresses a critical unmet need in the field. Dr. Padideh Kamali-Zare, Founder and CEO of Darmiyan, said that, "BrainSee is the first product of this vision, backed by our solid technological infrastructure capable of driving further transformations and scalable innovations in the brain health landscape." The test's early screening capabilities and risk stratification empower timely and personalized treatments for high-risk aMCI patients, potentially delaying dementia onset. Through taking away the need for expensive and invasive tests, BrainSee shifts the patient experience from prolonged anxiety to proactive management, aligning with emerging Alzheimer's treatments where accurate prognosis is crucial for determining suitable candidates. BrainSee's impact extends beyond patient care, offering significant economic benefits to healthcare stakeholders. By potentially reducing the billions of dollars spent annually on Alzheimer's care through effective management and treatment, the test promises a transformative impact on the industry. Previously granted FDA breakthrough designation in 2021, BrainSee stands out for its prognostic accuracy, patient convenience, same-day results, and seamless integration into clinical workflows. The global availability of MRI enhances its clinical utility, providing a paradigm shift in aMCI workup from invasive, non-specific, and costly biomarker-based methods to non-invasive and actionable forecasts of future improvement or progression. The FDA approval coincided with the JP Morgan HealthCare conference in San Francisco, and BrainSee is now accessible to physicians through a secure and HIPAA-compliant web portal. For more information, visit brainsee.ai . About Darmiyan: Darmiyan is a pioneering brain technology company based in San Francisco, California, their mission is to “leverage 40 years of cutting edge neuroscience research com bined with advanced medical image processing and advanced ML/AI to address the biggest healthcare challenge of our time: detecting neurodegenerative disease at early stages when treatments matter.” Author BioFocus Newsroom Previous Next