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iPSC-based Manufacture vs. Autologous Model Production Costs Examined via Financial Analysis

Autologous and allogeneic cell therapies are establishing viable clinical pathways but cannot be manufactured cost-effectively at scale. Manufacturing natural killer (NK) cell therapies, and possibly T-cell therapies, using induced pluripotent stem cells (iPSCs) is understood to be significantly more cost-effective. Now those cost advantages have been quantified.

Specifically, the cost of goods per treatment can be reduced as much as 95% when manufacturing via iPSCs rather than using traditional autologous or allogenic production methods. By decoupling production from the patient, manufacturers can benefit from large-scale batch production, standardized processes, less labor, and a less complex infrastructure than either autologous or allogeneic production. Details are spelled out in a white paper by Cellistic, based on an intense cost-of-goods analysis of NK cell therapy manufacturing performed by Astrid Van Damme, PhD, head of project management at Cellistic, for her MBA thesis.

In it, Van Damme advocates creating a universal master cell bank that feeds multiple working cell banks. Those working cell banks, in turn, generate intermediate hematopoietic stem cells that are differentiated into the final therapeutic product. “This cascade creates an essentially inexhaustible, standardized source material for the entire commercial lifecycle of the product,” she asserts.

Cellistic’s internal review compared seven economic drivers for each of the three cell therapy manufacturing options. Notable advantages for an iPSC manufacturing strategy include:

  • Commercial scale production
  • Exponential scale-up or scale-out
  • Industrial-scale reproducibility
  • Use of standard cold-chain logistics
  • Minimal patient interactions
  • Reduced patient attrition
  • Potentially global market reach

An iPSC manufacturing strategy for cell therapies drops the cost of goods sold to about $5,000 per dose, down from $115,000 per dose for autologous therapeutics and $40,000 per dose for allogeneic therapeutics, Van Damme reports.

Autologous and allogeneic manufacturing, in contrast, both have severe constraints that increase costs for manufacturers and payers alike. Materials and labor alone account for 50% to 70% of autologous cell therapies—roughly $80,000 to $150,000. That’s a huge driver for U.S. list prices that, for the oncology therapeutics Kymriah® and Carvykti®, are at or above an adoption-limiting $475,000 per dose. Even after factoring in regional pricing differences and payer discounts, the net per-dose costs to payers are still extremely high.

Compared to iPSC manufacturing at clinical scale (150 vials and 200 M cells per vial) and at commercial scale (450 vials with 400 M cells per vial), Van Damme indicates:

  • Labor costs constituted about 13% of the costs of goods (vs. about 70% for autologous methods)
  • Costs per vial drop approximately 40%
  • Fixed costs were diluted by a factor of three

“Once a minimum threshold of operational maturity and throughput is achieved, iPSC-based manufacturing economics become comparatively robust to routine operational variability,” the paper concludes.

The post iPSC-based Manufacture vs. Autologous Model Production Costs Examined via Financial Analysis appeared first on GEN – Genetic Engineering and Biotechnology News.

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Biopharma Adopting AI Despite Remaining GMP Compliance Questions

The biopharma industry is embracing artificial intelligence (AI) in manufacturing, even though questions remain about how best to use the technology in a GMP environment.

At least, so says Sanjay Konagurthu, PhD, senior director, science and innovation, pharma services, at Thermo Fisher Scientific, who argues that the key to successful AI adoption is a clear use case.

“As is true in most industries, adoption of AI and machine learning (ML) is real and accelerating across the biopharma industry. However, most use cases center around applications that augment teams without completely redefining a validated process, such as smarter quality and inspection workflows.

“We’re seeing that the hesitation isn’t so much reluctance to adopt AI as it is the practical constraints of operating in a good manufacturing practices-regulated environment. To adopt AI and ML in regulated environments, you need clear intended use, strong data foundations, traceable governance, and set parameters for disciplined control and monitoring,” he tells GEN.

Data foundations

In addition to establishing a strong use case, drug companies need an IT infrastructure that facilitates the flow of process data, according to Konagurthu, who says data silos are a persistent problem in biopharma.

“As with most scientific endeavors, vast quantities of data are generated across the biopharma industry, among labs, organizations, consortia, and nations, and much of this data is stored in a singular system. So, there’s a connectivity challenge, but that’s not the only reason why processing technologies struggle to exchange information.

“The data is often captured according to different standards and exists in a variety of formats, which means context is easily lost. Also, the data exists in a wide variety of structured and unstructured formats, which compounds the challenge in effective curation and analysis,” he says.

Failure to establish an effective infrastructure or standardize data has multiple negative consequences, Konagurthu adds.

“When data from early development can’t be connected through to commercialization, teams end up re-running experiments and analysis. They may even miss early signals that could impact downstream manufacturing or risk quality.

“When companies look to scale or implement new technologies like AI and ML, fragmented data can become prohibitive. Ultimately, for biopharma, this could extend the time it takes to bring a promising molecule to market,” he says.

Formul-AI-tion development

Beyond process development and control, formulation is another area where more and more biopharmaceutical companies are making a use case for AI.

Konagurthu says, “Biopharma scientists have historically used trial-and-error approaches to determine the right solubility and bioavailability of OSD [oral solid dose] therapies. With AI and ML models, teams can make earlier, better-informed decisions on formulation pathways.

“Early-stage acceleration in discovery and formulation echoes all the way into manufacturing and clinical supply, so improving the front end can compress timelines across the entire pipeline,” he adds.

The post Biopharma Adopting AI Despite Remaining GMP Compliance Questions appeared first on GEN – Genetic Engineering and Biotechnology News.

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Novel Targets for Complex Cancer Revealed by Genetic Regulatory Node Mapping

In a new study published in Nature titled, “Mapping convergent regulators of melanoma drug resistance by PerturbFate,” researchers from The Rockefeller University have developed a platform called PerturbFate that can systematically map how diverse disease-associated genetic variations reshape cells. By tracking gene regulation in single cells over time, the team identified regulatory nodes common to diverse variations. Using melanoma drug resistance as a proof-of-concept, results showed that these shared points of control offer a path toward combination therapies that can target disease across many genetic causes. 

“Once you know that a disease is associated with hundreds of genes, how do you design one therapy to target it?” posed Junyue Cao, PhD, head of the Laboratory of Single-Cell Genomics and Population Dynamics at Rockefeller. “We wondered whether all these different genes may be mediated by some shared downstream signaling that we can discover and target instead.” 

Advances in genomic sequencing and genetic screening have allowed researchers to identify hundreds of genetic mutations linked to disease. Yet these genes often span diverse pathways with broad functionalities, from gene regulation to cell signaling, making them difficult to target collectively.  

Cao proposed that if these mutations converge on shared downstream programs, the key challenge is not to target each mutation individually, but to identify the common control points known as regulatory nodes.  

PerturbFate allows researchers to observe how different genetic changes reshape a cell in real time by tracking DNA accessibility, and RNA production and processing. By capturing these changes in the same single cell, the system reveals the networks of genes that control cell behavior and how different genetic variations can have the same effect. 

“This technology lets us perturb hundreds to thousands of genes in parallel and then measure the detailed molecular changes in each individual cell,” says Cao. “That allows us to link many different genetic perturbations to their downstream effects and identify regulatory nodes.” 

To test the platform, the authors focused on melanoma drug resistance. Using PerturbFate, they selected 143 genes linked to resistance to the common melanoma drug, Vemurafenib. PerturbFate then tracked how deactivating each of these genes reshaped the cell. Cao explains the platform captures gene expression, RNA dynamics and chromatin state, all critical components when identifying upstream regulators that drive these disease states. 

After analyzing more than 300,000 cells, the researchers found that diverse genetic perturbations pushed melanoma cells into the same drug-resistant state. Drug resistance dropped significantly when these common control points were targeted, pointing to a promising strategy for combination therapies. 

The platform also revealed an important nuance involving the transcriptional coactivator, Mediator Complex. Disrupting different parts of this same complex could trigger drug resistance through routes that ultimately converged on the same survival signal in melanoma cells, called VEGFC. Resistant cells could no longer proliferate after blocking that signal. 

The team has made both the experimental and computational tools behind PerturbFate openly available, and plans to extend the approach from cultured cells to living systems. Cao and colleagues are currently applying PerturbFate to conditions, such as aging and Alzheimer’s disease, to uncover shared vulnerabilities that can guide more effective treatments. 

“This is just a starting point,” says Cao. “Now that we’ve demonstrated the approach in a simple model, we’re working to extend it into living systems to study even more complex diseases.” 

The post Novel Targets for Complex Cancer Revealed by Genetic Regulatory Node Mapping appeared first on GEN – Genetic Engineering and Biotechnology News.

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<![CDATA[Bupropion may cause dose-linked tinnitus; this case shows symptoms improve after dose reduction, helping manage depression without stopping treatment.]]>
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Earlier Surveillance Warranted for Young Cancer Survivors

Approximately one in six adolescents and young adults who survive cancer will be diagnosed with another cancer within 30 years of their initial diagnosis, making their cancer risk more than double that of the general population, shows data from Canada.

“When combined with the relatively high survival rates in this age range, at approximately 86%, there is a growing population of young cancer survivors that will be adversely affected by their cancer diagnosis and its treatment even decades later,” write Miranda Fidler-Benaoudia, a cancer epidemiologist at the University of Calgary Cumming School of Medicine and Cancer Care Alberta, and co-authors in the Canadian Medical Association Journal.

“Given that subsequent primary neoplasms are major contributors to morbidity and premature mortality, these findings underscore the need for innovative solutions to prevent, detect, and treat subsequent primary neoplasms among survivors of adolescent and young adult cancer,” they say.

Although global data suggest that adolescent and young adult cancer survivors are 1.6 to 4.3 times more likely to develop a subsequent cancer than expected in the general population, data are limited for Canada, where cancer rates among this group increased annually by 1.3% from 1998 to 2012, with an estimated 8739 adolescents and young adults diagnosed with cancer in 2022.

The Alberta Adolescent and Young Adult Cancer Survivor Study retrospectively reviewed data for 24,459 people with a neoplasm first diagnosed between 1983 and 2017 at age 15 to 39 years. Of these, 1442 (5.9%) had subsequent primary neoplasms, 1129 (7.6%) of which occurred among the 14,818 people who were five-year survivors.

The researchers report that, overall, adolescent and young adult cancer survivors were 2.2 times more likely to develop a subsequent primary neoplasm than would be expected in the general population, equating to 31.7 excess neoplasms per 10,000 person–years.

For five-year survivors, the incidence was twofold higher versus the general population with an excess risk of 35.7 per 10,000 person–years.

The greatest excess risks occurred among survivors of breast cancer (85.8 per 10,000 person–years), lymphomas other than Hodgkin lymphoma or non-Hodgkin lymphoma (82.0 per 10,000 person–years), and oral cavity, lip, and pharyngeal cancer (74.7 per 10,000 person–years).

Conversely, no significant excesses were observed for survivors of acute myeloid leukemia, central nervous system cancers, ovarian cancer, nonovarian and nontesticular gonadal and related tumors, stomach cancer, lung, bronchial, and tracheal cancer, and endometrial cancer.

After five-year survival, the 30-year cumulative incidence of a subsequent primary neoplasm was 17.7% overall, with incidence highest among survivors of cancers of the oral cavity, lip, or pharynx (28.9%), breast cancer (27.3%), colon cancer (23.5%), and Hodgkin lymphoma (22.7%).

Importantly, the team found that the absolute difference in cumulative incidence between the survivors and general population grew as time since diagnosis increased; for example, for five-year survivors of breast cancer, the absolute difference was 2.9% at 10 years postdiagnosis compared with 12.7% at 30 years postdiagnosis.

“Although people with nearly all types of adolescent and young adult cancer investigated were at an increased risk of developing a subsequent primary neoplasm, survivors of Hodgkin lymphoma and breast cancer were identified as particularly vulnerable populations, with nearly one-third of subsequent primary neoplasms occurring after five-year survival diagnosed in these survivor groups,” Fidler-Benaoudia et al remark. “These findings are consistent with previous studies and reflect the established late effects of radiotherapy, chemotherapy, and hormone therapy.”

However, they also note that genetic factors may play a role, and that genetic counseling and education on maintaining healthy lifestyles are important in caring for survivors.

The most common subsequent primary neoplasms were breast (27.1%), digestive (11.9%), hematopoietic (10.6%), or respiratory (6.8%) cancers, together accounting for nearly 60% of subsequent primary neoplasms.

Fidler-Benaoudia and colleagues say that their findings “offer valuable directions for research and cancer control.”

They point out that at present there are no risk-based survivorship care guidelines that cover the entire age range of the adolescent and young adult cancer population.

“Although both pediatric and adolescent and young adult cancer survivors are at increased risks for late effects, the magnitude of these risks varies and implications for care can differ; thus, clinical investigations that assess the association of treatment exposures with late effects like subsequent primary neoplasms should be a research priority,” the authors write.

They also stress that further work is needed to expand inclusion criteria for early high-risk screening initiatives and to develop specialized treatment guidelines that balance curing the subsequent primary neoplasm while effectively managing the survivors’ late effects.

The post Earlier Surveillance Warranted for Young Cancer Survivors appeared first on Inside Precision Medicine.

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Syncing Exercise to Body Clock Maximizes Cardiovascular Benefits

Timing exercise according to a person’s natural propensity towards being a “morning lark” or an “night owl” could maximize its cardiovascular benefits, a randomized trial suggests.

Matching exercise according to individual body clocks maximized the sleep quality and several parameters of cardiovascular health of middle-aged adults with preclinical risk factors.

The findings highlight the added value of incorporating circadian biology into exercise plans to optimize health outcomes.

Reporting their findings in Open Heart, the researchers suggest that assessing for chronotype—the predisposition towards morningness or eveningness—should be considered when prescribing exercise for those at risk of cardiometabolic disease.

“Our study shows that when you exercise may be just as important as how you exercise,” researcher Arsalan Tariq, PhD, from the University of Lahore, explained to Inside Precision Medicine.

“Aligning workouts with an individual’s biological clock significantly amplifies cardiovascular and metabolic benefits, offering a simple way to personalize prevention and improve adherence.”

A person’s chronotype affects their sleeping patterns, hormonal secretion, and energy levels during the day through an internal timing mechanism.

This is regulated by the circadian clock in a system that influences various physiological processes including blood pressure, heart rate, glucose metabolism, and vascular function.

Tariq and team examined how timing exercise affected key indicators of cardiovascular health among at-risk middle-aged adults.

Participants were aged 40 to 60 years and had at least one cardiovascular risk factor, such as high blood pressure, overweight, or obesity. The group also included those with a family history of premature cardiovascular disease.

Participants were randomly assigned to exercise at a time that either matched or did not match their chronotype, between 8am and 11am or between 6pm and 9pm.

This consisted of five, 40-minute sessions per week of supervised moderate intensity aerobic exercise such as brisk or treadmill walking for 12 weeks.

Of the 134 participants who completed the 60 sessions, 70 were larks—34 of whom had exercise matched with chronotype—and 64 were owls, with 30 matched to chronotype.

Measurements taken at the start of the trial and three days after it finished showed particular improvements in sleep and systolic blood pressure among those matched with chronotype.

Sleep quality improved by 3.4 points in matched participants versus 1.2 in the unmatched on the Pittsburgh Sleep quality Index. Systolic blood pressure dropped by 10.8 mmHg compared with 5.5mmHg in matched versus unmatched groups, respectively.

Chronotype-aligned exercise also led to significantly greater improvements in diastolic blood pressure, heart rate variability, peak oxygen consumption, low-density lipoprotein, and fasting glucose compared with misaligned exercise.

“Personalized, time-matched exercise interventions may become a practical strategy in clinical and public health settings, potentially leading to better outcomes and improved engagement,” the researchers reported.

“Future research and guidelines may consider circadian factors as a core component of lifestyle-based disease prevention.”

The post Syncing Exercise to Body Clock Maximizes Cardiovascular Benefits appeared first on Inside Precision Medicine.

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Development of a Contextualized, Research-Based Flemish Assessment Framework for Digital Care, Assistance, and Support: Delphi Study

<strong>Background:</strong> The rapid evolution of digital technologies has transformed health, mental health, and social care, offering new modalities of digital care, assistance, and support through web-based platforms, mobile apps, extended reality, wearables, and artificial intelligence systems. Despite this proliferation, there is little consensus on what constitutes “high-quality” digital care. Challenges persist regarding data security, interoperability, accessibility, sustainability, and professional competence, whereas existing standards and regulations provide fragmented guidance. <strong>Objective:</strong> This study aimed to develop a contextualized, consensus-based quality assessment framework for digital care, assistance, and support in Flanders, Belgium. For this purpose, perspectives across technology, organizational processes, and professional competencies were integrated. <strong>Methods:</strong> The study used a multiphase design comprising (1) 10 expert interviews with Flemish government officials; (2) a narrative literature review of 303 peer-reviewed and gray literature sources; (3) a 3-round Delphi study with 50 experts across 5 domains (end users, facilitators, technology developers, deontology and ethics experts, and digital inclusion and media literacy experts); and (4) 4 complementary focus groups and 3 interviews with specialists in artificial intelligence, regulation, social work, mental health, and IT. The Delphi rounds gathered iterative feedback through open-ended elicitation, structured rating, and classification of quality criteria. Quantitative data were analyzed using descriptive statistics, whereas qualitative feedback was subjected to thematic analysis. <strong>Results:</strong> A total of 50 experts participated in round 1, a total of 40 (80%) participated in round 2, and 27 (54%) participated in round 3. Round 1 generated 577 unique quality criteria, consolidated into 26 clusters organized under 3 pillars: technology, organization, and professional competencies. The relative importance across pillars was balanced (mean score 37.29, SD 12.38 for technology; 33.33, SD 10.39 for professional competencies; and 29.80, SD 10.45 for organizations). Accessibility, reliability, and safety ranked highest for the technology; vision, quality monitoring, and infrastructure ranked highest for organization; and support, digital competencies, and ethics ranked highest for professional competencies. The finalized framework included 112 criteria, of which 35 (31.3%) were designated as optional and 77 (68.8%) were designated as minimum requirements. Focus groups and interviews validated the framework’s comprehensiveness and usability, emphasizing proportional implementation, user centrality, and alignment with European Union regulations. Stakeholders highlighted the need for tools, training, and governance mechanisms to ensure adoption and sustainability. <strong>Conclusions:</strong> This study produced a codeveloped, context-sensitive quality assessment framework that balances technological robustness, organizational readiness, and professional competence in digital care, assistance, and support. The framework can serve both as a quality safeguard and a developmental road map. Accompanying self-assessment and governance tools enhance practical applicability. Implementation success will depend on governmental support, resource allocation, and structured feedback loops. Future research should pilot the framework in real-world settings, assess its impact, and establish mechanisms for continuous updates to maintain relevance in a rapidly evolving digital landscape. <strong>Trial Registration:</strong>
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<![CDATA[Experts share more on research developments of remternetug for Alzheimer disease.]]>
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STAT+: Novartis CEO joins Anthropic’s board

Want to stay on top of the science and politics driving biotech today? Sign up to get our biotech newsletter in your inbox.

Good morning. A reminder that if you’re ever feeling down about a mistake you made, there is always a way to turn it around — like how this delivery robot company has turned the issue of its robot crashing into my local bus stop into a marketing opportunity.

The need-to-know this morning

  • Revolution Medicines raised $2 billion in concurrent stock and debt offerings. The mammoth financings — double what the company intended to raise — come just days after daraxonrasib, its experimental treatment for advanced pancreatic cancer, was shown to double the median overall survival of patients in a Phase 3 clinical trial.

Bain Capital again creates a startup with older pharma drugs

After Bain Capital last summer said it licensed five immunology drugs from Bristol Myers Squibb, it’s now unveiling the company to take those treatments forward: a startup called Beeline Medicines.

Continue to STAT+ to read the full story…