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Pushing the Performance of Liquid Biopsies for Cancer with Nanotechnology

Nanotechnology opens the door to a range of unique methods for sensing cancer biomarkers in body fluids, thanks to the unusual properties and capabilities…

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By Mike May, PhD

Katherine Dunn, DPhil
senior lecturer
University of Edinburgh

Blood tests play a crucial role in diagnosing cancer and tracking the impact of a treatment, but their potential far outstrips their current uses. For example, the cellular composition of a blood sample may suggest that a patient has leukemia or lymphoma, but for solid tumors, diagnosis traditionally depends on analyzing a piece from a tumor biopsy. With a liquid biopsy, though, scientists look for signs of a tumor in the blood or other bodily fluids.1 As Katherine Dunn, DPhil, senior lecturer at the University of Edinburgh in the U.K., explains, “Liquid biopsies could be transformative for cancer patients, enabling the state of their tumors to be monitored more easily.”

Solid tumors shed cancer cells, tiny pieces of DNA, tumor-related vesicles, and so on. A liquid biopsy identifies and analyzes that information. That’s not easy to do, especially given that some of those cellular and molecular signals make up such a small fraction of the blood that even identifying them verges on the impossible. Indeed, for many years, it was.

Still, extensive efforts around the world have explored the potential of liquid biopsies in oncology. A team of scientists from the State Key Laboratory of Complex Severe and Rare Diseases in Beijing, China, performed a bibliometric analysis of articles on this topic over the past 11 years and found 6,331 articles from scientists in 95 countries and more than 7,000 institutions.2 As these researchers concluded: “The field is entering a phase of rapid development.”

Although many methods of performing a liquid biopsy exist today, better biopsies would be very useful in the clinic. “New approaches would help to make analysis of liquid biopsies quicker and more routine,” Dunn says.

But what technology could make lipid biopsies better? “Nanotechnology opens the door to a range of unique methods for sensing cancer biomarkers in body fluids, thanks to the unusual properties and capabilities of nanoscale systems,” Dunn explains. “Eventually, nanotechnology-based devices could be used for rapid analysis of liquid biopsies at the point of care, providing patients and their doctors with information to guide treatment plans.”

Huge benefits from tiny technology

Just what makes a technology nano? In general, the term means that some dimension of the technology is just nanometers—millionths of a meter—in size. To give some idea of how small that is, a piece of 20-pound printer paper is more than 100,000 nanometers thick.

Nanotechnology appears in many applications, from materials and sensors to information technology and medicine. One of the most recent and widely publicized uses of nanotechnology was in some of the vaccines for COVID-19, which delivered their payloads in lipid nanoparticles.

Janusz Rak MD, PhD
Jack Cole Chair
Pediatric Hematology/Oncology
McGill University

There are several major benefits of applying nanotechnology to liquid biopsies, says Janusz Rak, MD, PhD, Jack Cole Chair in Pediatric Hematology/Oncology at McGill University in Canada. For instance, “Some, perhaps most, of the liquid biopsy analytes—carriers of diagnostic information—are not soluble molecules, but nanoparticles, such as exosomes and other extracellular vesicles, are.” As a result, it’s easier to work with liquid biopsies bases on nanoparticles.

Rak also points out that many types of information can be combined in nanoparticles. “For example, they can contain informative RNA, or mutant DNA plus membrane proteins that can tell one what cells the DNA may be coming from,” he notes. Therefore, “particles can be analyzed in ways that extract information from their complexity, something that a protein or DNA fragment in blood will not have.”

Cell-based biopsies

For years, scientists have worked to develop liquid biopsies of cancer based on circulating tumor cells (CTCs), which were first reported by Australian pathologist T.R. Ashworth in 1869.3 In the more than 150 years since Ashworth’s discovery of CTCs, many studies looked for ways to identify and make use of these cells.

As explained by Shaobing Zhou, PhD, professor of material science and engineering at Southwest Jiaotong University in Chengdu, China, and his colleagues: “Escaping from primary tumors and entering into blood flow, circulating tumor cells (CTCs) contain significant information for both the original tumors and metastasis mechanisms.”4 Among the various potential uses of CTC-based liquid biopsies, these scientists noted the “great promise in early cancer detection, disease monitoring, prognosis and personalized medicine.” Zhou’s team also pointed out the potential value of nanotechnology-based approaches.

Recently, Seungpyo Hong, PhD, Milton J. Henrichs Chair and director of the Wisconsin Center for NanoBioSystems at the University of Wisconsin-Madison, and his colleagues developed a CTC-based liquid biopsy for gastrointestinal cancer.5 Using an approach that included a nanostructured surface and a machine-learning algorithm, these scientists developed a liquid biopsy that correctly identifies CTCs from gastrointestinal cancer 82.9% of the time. Moreover, the team reported that results from this liquid biopsy collected three months after treatment predicted the progression of the disease. The researchers concluded: “This approach to quantifying CTC abundance may be a clinically impactful in the timely determination of gastrointestinal cancer progression or response to treatment.”

Seeking circulating DNA

Rather than whole cells, much of the work on liquid biopsies for cancer looks for circulating tumor DNA (ctDNA), a form of cell-free DNA (cfDNA) that comes from tumor cells. “ctDNA characteristics such as sequence and methylation state can provide insights into cancers,” Dunn’s doctoral student Nathan Wu and his colleagues wrote.6 “The concentration of ctDNA in blood indicates tumour size and can quantify disease burden to monitor or predict treatment efficacy.”

Although ctDNA can be detected with next-generation sequencing or assays based on PCR, Dunn and her collaborators noted that these techniques “can be time consuming and complex.” Alternatively, the scientists pointed out, “Nanotechnology may enable simpler, cheaper, faster ctDNA diagnostics.”

Even with advances in nanotechnology-based liquid biopsies, the scarcity of ctDNA in blood remains a problem. As one potential solution, Sangeeta Bhatia, MD, PhD, John J. and Dorothy Wilson Professor at MIT, and her colleagues discovered a way to raise the levels of ctDNA. Usually, cells clear ctDNA from the blood, but Bhatia’s team reported on “an intravenous priming agent that is given prior to a blood draw to increase the abundance of cfDNA in circulation.”7 As these scientists explained, the “priming agent consists of nanoparticles that act on the cells responsible for cfDNA clearance to slow down cfDNA uptake.” In mice with tumors, this agent increased the sensitivity of a ctDNA assay from 0% to 75%. Bhatia’s team concluded: “We envision that this priming approach will significantly improve the performance of liquid biopsies across a wide range of clinical applications in oncology and beyond.”

The value of vesicles

Extracellular vesicles (EVs) released by tumors carry information about cancer.8 To analyze EVs, Sara Mahshid, PhD, assistant professor of bioengineering at McGill, and her colleagues developed a device, called a MoSERS microchip, that traps EVs in nanocavities where the EVs can be analyzed.

Rak, Mahshid, and their colleagues used the MoSERS microchip to study EVs produced by a deadly brain cancer, glioblastoma.9 Using this technology, Rak says, “we were able to differentiate cancer patients and healthy individuals.” In fact, by analyzing the data from the MoSERS microchip with a neural network, the scientists accurately diagnosed 87% of the patients.

EVs can be used in liquid biopsies for many cancers beyond the brain. For instance, Edwin Posadas, MD, director of the experimental therapeutics program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center in Los Angeles, and his colleagues used a nanosurface to capture EVs produced by prostate cancer.10 From this, the scientists developed a liquid biopsy that reveals if a patient’s disease is still local or has metastasized. As Posadas and his colleagues reported: “This assay may complement current imaging tools and blood-based tests for timely detection of metastatic progression that can improve care for [prostate cancer] patients.”

The nanoscience of sensors

At the University of Naples Federico II in Italy, Stefano Cinti, PhD, associate professor of analytical chemistry, and his colleagues develop nanotechnology-based sensors and biosensors. “I work in the field of diagnostics, and I develop point-of-care devices at my research group, uninanobiosensors.com,” Cinti says. “In particular, we develop electrochemical biosensors that are similar to the glucose strips for diabetes patients.”

Stefano Cinti
Stefano Cinti, PhD
assoc. professor in analytical chemistry
University of Naples Federico II

This work’s foundation is in nanotechnology. “Here, the adoption of nanotechnology, in particular nanomaterials, is fundamental to develop very sensitive and affordable diagnostic devices that would not be as sensitive with traditional materials, such as gold nanoparticles versus bulk gold,” Cinti explains.

In particular, Cinti and his colleagues work on liquid biopsies to detect miRNAs circulating in the blood of patients with breast cancer.11 “We develop our printed electrochemical strips, and the adoption of gold nanoparticles gives us the possibility to both immobilize a recognition probe for the miRNA and to increase the conductivity of the strips, thus improving selectivity and sensitivity towards the target of interests,” Cinti says.

This work, like other liquid biopsies, faces a crucial obstacle. “The main challenges in developing a liquid biopsy on chip is related to the low amount of circulating miRNA, just like other biomarkers like cells, proteins, [and] exosomes,” Cinti explains. “The real challenge is to develop very sensitive architectures that can detect one molecule of interest within interference, without making the system too complex.” To reduce the complexity as much as possible, Cinti and his colleagues use paper-based substrates for sensors. “The use of porous materials, like paper-based ones, allow an all-in-one platform that is able to store reagents, remove interference, and pre-concentrate real samples, thus improving sensitivity and real-world applications.”12

nanotechnology illustration
At the University of Naples Federico II, Stefano Cinti uses nanotechnology to develop a range of sensors and biosensors that can be used in liquid biopsies applied to diagnostics aimed at various analytes.

Other research teams also apply nanotechnology in the development of sensors that can be applied to liquid biopsies. At the Toronto Metropolitan University, Bo Tan, a professor who studies various uses of nanotechnology, and her colleagues developed a 3D nanosensor.13 From just 5 microliters of blood serum, the sensor collected data that was analyzed with a neural network. According to the scientists, “Detection of primary and secondary tumor achieved 100% accuracy. Prediction of intracranial tumor location achieved 96% accuracy.”

Technology from teamwork

Making the most of nanotechnology in liquid biopsies depends on a combination of expertise and equipment. The biggest challenges of applying nanotechnology to these assays, Rak says, “range from inherent dimensions of nanoparticles and access to nanotechnologies required to work with them, to the inner complexity of particles and methods of exploiting it—for example, by AI.”

To address those challenges, Rak and his colleagues created the Center for Applied Nanomedicine, described as “an environment that would support a community of researchers aiming to collaborate, exchange expertise, share and maintain state-of-the-art equipment in order to advance extracellular vesicle and nanomedicine science across a broad spectrum of basic and translational biomedical research areas.”14

Developing a new liquid biopsy also depends on tools to validate the assays. As explained by the U.S. National Institute of Standards and Technology (NIST): “Reference materials are needed to help develop, validate, and ensure the quality of new cancer biomarker assays.”15 To assist scientists with such validation, NIST “developed a platform to produce customized NIST ctDNA test materials.”

Another resource is the U.S. National Cancer Institute’s (NCI’s) Liquid Biopsy Consortium.16 According to the institute’s website, this partnership between academic, industrial, and government segments was “designed to advance and validate liquid biopsy technologies specifically targeted for early stage cancer detection … [and] methods to distinguish cancer from benign disease; or aggressive from indolent cancers.”

In addition to improving the nanotechnology behind liquid biopsies, scientists seek better ways to analyze the data. Many teams take on that challenge. As one example, Gavin Ha, PhD, a computational scientist at the Fred Hutchinson Cancer Center in Seattle, and his colleagues developed a collection of tools for analyzing cfDNA data. One of those tools, called Griffin, helps scientists analyze gene-expression information available in cfDNA. As Ha and his colleagues reported: “Griffin is a framework for accurate tumor subtyping and can be generalizable to other cancer types for precision oncology applications.”17

Beyond the technological challenges, Rak points out others: “There are also biomedical challenges surrounding the amounts of relevant nanoparticles in liquid biopsy samples, sensitivity and specificity of detection, and multiple other questions.”

A hefty horizon

The current status of liquid biopsies is only the beginning of this field’s appeal and applications. The primary of this field should always be improving the lives of patients with cancer. Still, the financial incentive should not be ignored.

Three years ago, a team of investment experts from New York-based TD Cowen noted: “We estimate that the market opportunity across all classes of liquid biopsies ranges between at least $30B and $130B in the United States alone.”18 In addition, the TD Cowen team pointed out the range of opportunities ahead to expand the clinical use of liquid biopsies: “The opportunity remains large, promising, and under-penetrated—especially in the clinical setting. Liquid biopsy tools for cancer screening and survival monitoring are only now advancing towards market commercialization. Penetration of the therapeutic selection market is well below 10%.”

Despite its many challenges, nanotechnology offers many opportunities to improve existing liquid biopsies and develop new ones. During the more than a century and a half since Ashworth first identified CTCs, scientists have taken a wide range of approaches to develop liquid biopsies that detect and often quantify signs of cancer. In the next 150 years, nanotechnology of various sorts, typically supported by advanced methods of data analysis, will surely reveal aspects of cancer and enhance new treatments in ways that Ashworth could not have imagined.

 

References

  1. Pantel, K., Alix-Panabières, C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends in Molecular Medicine, 16:398–406. (2010).
  2. Jiang, S., Liu, Y., Xu, Y., et al. Research on liquid biopsy for cancer: A bibliometric analysis. Heliyon, 9(3):e14145. (2023).
  3. Ashworth, T. R. A case of cancer in which cells similar to those in the tumors were seen in the blood after death. The Australasian Medical Journal. 14:146–149 (1869).
  4. Hou, J., Liu, X., Zhou, S. Programmable materials for efficient CTCs isolation: from micro/nanotechnology to biomimicry. View, 2(6):20200023. (2021).
  5. Poellmann, M.J., Bu, J., Liu, S., et al. Nanotechnology and machine learning enable circulating tumor cells as a reliable biomarker for radiotherapy responses of gastrointestinal cancer patients. Biosensors and Bioelectronics, 226L115117. (2023).
  6. Wu, N.J.W., Aquilina, M., Qian, B-Z., et al. The application of nanotechnology for quantification of circulating tumour DNA in liquid biopsies: a systematic review. IEEE Reviews in Biomedical Engineering, 16:499–513. (2023).
  7. Martin-Alonso, C., Tabrizi, S., Xiong, K., et al. A nanoparticle priming agent reduces cellular uptake of cell-free DNA and enhances the sensitivity of liquid biopsies. bioRxiv. (2023).
  8. Rak, J., Strzadal, L. Heterogeneity of extracellular vesicles and particles: molecular voxels in the blood borne “hologram” of organ function, disfunction and cancer. Archivum Immunologiae et Therapiae Experimentalis, 72(1):5. (2023).
  9. Jalali, M., Mata, C.d.R., Montermini, L., et al MoS2-Plasmonic Nanocavities for Raman Spectra of Single Extracellular Vesicles Reveal Molecular Progression in Glioblastoma. ACS Nano, 17(13):12052–12071. (2023).
  10. Wang, J., Sun, N., Lee, Y-T., et al. Prostate cancer extracellular vesicle digital scoring assay—a rapid noninvasive approach for quantification of disease-relevant mRNAs. Nanotoday. 48:101746. (2023).
  11. 11. Singh, S., Miglione, A., Raucci, A., et al. Towards sense and sensitivity-based electrochemical biosensors for liquid biopsy-based breast cancer detection. TrAC Trends in Analytical Chemistry, 163: 117050. (2023).
  12. Singh, S., Podder, P. S., Russo, M., et al. Tailored point-of-care biosensors for liquid biopsy in the field of oncology. Lab on a Chip, 23(1):44–61. (2023).
  13. Premachandran, S., Haldavnekar, R.,  Das, S., et al. DEEP surveillance of brain cancer using self-functionalized 3D nanoprobes for noninvasive liquid biopsy. ACS Nano, 16(11):17948–17964. (2022).
  14. Centre for Applied Nanomedicine.
  15. National Institute of Standards and Technology. Cancer biomarker measurements and collaborations. (Updated May 16, 2023).
  16. U.S. National Cancer Institute. Liquid Biopsy Consortium.
  17. Doebley, A-L., Ko, M., Liao, H., et al. A framework for clinical cancer subtyping from nucleosome profiling of cell-free DNA. Nature Communication, 13:7475. (2022).
  18. Schenkel, D., Nambi, S., Blicker, R., Lin, Chris. Liquid biopsy: early detection of a huge investment opportunity. (2020).

 

Mike May is a freelance writer and editor with more than 30 years of experience. He earned an MS in biological engineering from the University of Connecticut and a PhD in neurobiology and behavior from Cornell University. He worked as an associate editor at American Scientist, and he is the author of more than 1,000 articles for clients that include GEN, Nature, Science, Scientific American, and many others. In addition, he served as the editorial director of many publications, including several Nature Outlooks and Scientific American Worldview.

The post Pushing the Performance of Liquid Biopsies for Cancer with Nanotechnology appeared first on Inside Precision Medicine.

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Four burning questions about the future of the $16.5B Novo-Catalent deal

To build or to buy? That’s a classic question for pharma boardrooms, and Novo Nordisk is going with both.
Beyond spending billions of dollars to expand…

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To build or to buy? That’s a classic question for pharma boardrooms, and Novo Nordisk is going with both.

Beyond spending billions of dollars to expand its own production capacity for its weight loss drugs, the Danish drugmaker said Monday it will pay $11 billion to acquire three manufacturing plants from Catalent. It’s part of a broader $16.5 billion deal with Novo Holdings, the investment arm of the pharma’s parent group, which agreed to acquire the contract manufacturer and take it private.

It’s a big deal for all parties, with potential ripple effects across the biotech ecosystem. Here’s a look at some of the most pressing questions to watch after Monday’s announcement.

Why did Novo do this?

Novo Holdings isn’t the most obvious buyer for Catalent, particularly after last year’s on-and-off M&A interest from the serial acquirer Danaher. But the deal could benefit both Novo Holdings and Novo Nordisk.

Novo Nordisk’s biggest challenge has been simply making enough of the weight loss drug Wegovy and diabetes therapy Ozempic. On last week’s earnings call, Novo Nordisk CEO Lars Fruergaard Jørgensen said the company isn’t constrained by capital in its efforts to boost manufacturing. Rather, the main challenge is the limited amount of capabilities out there, he said.

“Most pharmaceutical companies in the world would be shopping among the same manufacturers,” he said. “There’s not an unlimited amount of machinery and people to build it.”

While Novo was already one of Catalent’s major customers, the manufacturer has been hamstrung by its own balance sheet. With roughly $5 billion in debt on its books, it’s had to juggle paying down debt with sufficiently investing in its facilities. That’s been particularly challenging in keeping pace with soaring demand for GLP-1 drugs.

Novo, on the other hand, has the balance sheet to funnel as much money as needed into the plants in Italy, Belgium, and Indiana. It’s also struggled to make enough of its popular GLP-1 drugs to meet their soaring demand, with documented shortages of both Ozempic and Wegovy.

The impact won’t be immediate. The parties expect the deal to close near the end of 2024. Novo Nordisk said it expects the three new sites to “gradually increase Novo Nordisk’s filling capacity from 2026 and onwards.”

As for the rest of Catalent — nearly 50 other sites employing thousands of workers — Novo Holdings will take control. The group previously acquired Altasciences in 2021 and Ritedose in 2022, so the Catalent deal builds on a core investing interest in biopharma services, Novo Holdings CEO Kasim Kutay told Endpoints News.

Kasim Kutay

When asked about possible site closures or layoffs, Kutay said the team hasn’t thought about that.

“That’s not our track record. Our track record is to invest in quality businesses and help them grow,” he said. “There’s always stuff to do with any asset you own, but we haven’t bought this company to do some of the stuff you’re talking about.”

What does it mean for Catalent’s customers? 

Until the deal closes, Catalent will operate as a standalone business. After it closes, Novo Nordisk said it will honor its customer obligations at the three sites, a spokesperson said. But they didn’t answer a question about what happens when those contracts expire.

The wrinkle is the long-term future of the three plants that Novo Nordisk is paying for. Those sites don’t exclusively pump out Wegovy, but that could be the logical long-term aim for the Danish drugmaker.

The ideal scenario is that pricing and timelines remain the same for customers, said Nicole Paulk, CEO of the gene therapy startup Siren Biotechnology.

Nicole Paulk

“The name of the group that you’re going to send your check to is now going to be Novo Holdings instead of Catalent, but otherwise everything remains the same,” Paulk told Endpoints. “That’s the best-case scenario.”

In a worst case, Paulk said she feared the new owners could wind up closing sites or laying off Catalent groups. That could create some uncertainty for customers looking for a long-term manufacturing partner.

Are shareholders and regulators happy? 

The pandemic was a wild ride for Catalent’s stock, with shares surging from about $40 to $140 and then crashing back to earth. The $63.50 share price for the takeover is a happy ending depending on the investor.

On that point, the investing giant Elliott Investment Management is satisfied. Marc Steinberg, a partner at Elliott, called the agreement “an outstanding outcome” that “clearly maximizes value for Catalent stockholders” in a statement.

Elliott helped kick off a strategic review last August that culminated in the sale agreement. Compared to Catalent’s stock price before that review started, the deal pays a nearly 40% premium.

Alessandro Maselli

But this is hardly a victory lap for CEO Alessandro Maselli, who took over in July 2022 when Catalent’s stock price was north of $100. Novo’s takeover is a tacit acknowledgment that Maselli could never fully right the ship, as operational problems plagued the company throughout 2023 while it was limited by its debt.

Additional regulatory filings in the next few weeks could give insight into just how competitive the sale process was. William Blair analysts said they don’t expect a competing bidder “given the organic investments already being pursued at other leading CDMOs and the breadth and scale of Catalent’s operations.”

The Blair analysts also noted the companies likely “expect to spend some time educating relevant government agencies” about the deal, given the lengthy closing timeline. Given Novo Nordisk’s ascent — it’s now one of Europe’s most valuable companies — paired with the limited number of large contract manufacturers, antitrust regulators could be interested in taking a close look.

Are Catalent’s problems finally a thing of the past?

Catalent ran into a mix of financial and operational problems over the past year that played no small part in attracting the interest of an activist like Elliott.

Now with a deal in place, how quickly can Novo rectify those problems? Some of the challenges were driven by the demands of being a publicly traded company, like failing to meet investors’ revenue expectations or even filing earnings reports on time.

But Catalent also struggled with its business at times, with a range of manufacturing delays, inspection reports and occasionally writing down acquisitions that didn’t pan out. Novo’s deep pockets will go a long way to a turnaround, but only the future will tell if all these issues are fixed.

Kutay said his team is excited by the opportunity and was satisfied with the due diligence it did on the company.

“We believe we’re buying a strong company with a good management team and good prospects,” Kutay said. “If that wasn’t the case, I don’t think we’d be here.”

Amber Tong and Reynald Castañeda contributed reporting.

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Petrina Kamya, Ph.D., Head of AI Platforms at Insilico Medicine, presents at BIO CEO & Investor Conference

Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb….

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Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb. 26-27 at the New York Marriott Marquis in New York City. Dr. Kamya will speak as part of the panel “AI within Biopharma: Separating Value from Hype,” on Feb. 27, 1pm ET along with Michael Nally, CEO of Generate: Biomedicines and Liz Schwarzbach, PhD, CBO of BigHat Biosciences.

Credit: Insilico Medicine

Petrina Kamya, PhD, Head of AI Platforms and President of Insilico Medicine Canada, will present at the BIO CEO & Investor Conference happening Feb. 26-27 at the New York Marriott Marquis in New York City. Dr. Kamya will speak as part of the panel “AI within Biopharma: Separating Value from Hype,” on Feb. 27, 1pm ET along with Michael Nally, CEO of Generate: Biomedicines and Liz Schwarzbach, PhD, CBO of BigHat Biosciences.

The session will look at how the latest artificial intelligence (AI) tools – including generative AI and large language models – are currently being used to advance the discovery and design of new drugs, and which technologies are still in development. 

The BIO CEO & Investor Conference brings together over 1,000 attendees and more than 700 companies across industry and institutional investment to discuss the future investment landscape of biotechnology. Sessions focus on topics such as therapeutic advancements, market outlook, and policy priorities.

Insilico Medicine is a leading, clinical stage AI-driven drug discovery company that has raised over $400m in investments since it was founded in 2014. Dr. Kamya leads the development of the Company’s end-to-end generative AI platform, Pharma.AI from Insilico’s AI R&D Center in Montreal. Using modern machine learning techniques in the context of chemistry and biology, the platform has driven the discovery and design of 30+ new therapies, with five in clinical stages – for cancer, fibrosis, inflammatory bowel disease (IBD), and COVID-19. The Company’s lead drug, for the chronic, rare lung condition idiopathic pulmonary fibrosis, is the first AI-designed drug for an AI-discovered target to reach Phase II clinical trials with patients. Nine of the top 20 pharmaceutical companies have used Insilico’s AI platform to advance their programs, and the Company has a number of major strategic licensing deals around its AI-designed therapeutic assets, including with Sanofi, Exelixis and Menarini. 

 

About Insilico Medicine

Insilico Medicine, a global clinical stage biotechnology company powered by generative AI, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques for novel target discovery and the generation of novel molecular structures with desired properties. Insilico Medicine is developing breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system diseases, infectious diseases, autoimmune diseases, and aging-related diseases. www.insilico.com 


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Another country is getting ready to launch a visa for digital nomads

Early reports are saying Japan will soon have a digital nomad visa for high-earning foreigners.

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Over the last decade, the explosion of remote work that came as a result of improved technology and the pandemic has allowed an increasing number of people to become digital nomads. 

When looked at more broadly as anyone not required to come into a fixed office but instead moves between different locations such as the home and the coffee shop, the latest estimate shows that there were more than 35 million such workers in the world by the end of 2023 while over half of those come from the United States.

Related: There is a new list of cities that are best for digital nomads

While remote work has also allowed many to move to cheaper places and travel around the world while still bringing in income, working outside of one's home country requires either dual citizenship or work authorization — the global shift toward remote work has pushed many countries to launch specific digital nomad visas to boost their economies and bring in new residents.

Japan is a very popular destination for U.S. tourists. 

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This popular vacation destination will soon have a nomad visa

Spain, Portugal, Indonesia, Malaysia, Costa Rica, Brazil, Latvia and Malta are some of the countries currently offering specific visas for foreigners who want to live there while bringing in income from abroad.

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With the exception of a few, Asian countries generally have stricter immigration laws and were much slower to launch these types of visas that some of the countries with weaker economies had as far back as 2015. As first reported by the Japan Times, the country's Immigration Services Agency ended up making the leap toward a visa for those who can earn more than ¥10 million ($68,300 USD) with income from another country.

The Japanese government has not yet worked out the specifics of how long the visa will be valid for or how much it will cost — public comment on the proposal is being accepted throughout next week. 

That said, early reports say the visa will be shorter than the typical digital nomad option that allows foreigners to live in a country for several years. The visa will reportedly be valid for six months or slightly longer but still no more than a year — along with the ability to work, this allows some to stay beyond the 90-day tourist period typically afforded to those from countries with visa-free agreements.

'Not be given a residence card of residence certificate'

While one will be able to reapply for the visa after the time runs out, this can only be done by exiting the country and being away for six months before coming back again — becoming a permanent resident on the pathway to citizenship is an entirely different process with much more strict requirements.

"Those living in Japan with the digital nomad visa will not be given a residence card or a residence certificate, which provide access to certain government benefits," reports the news outlet. "The visa cannot be renewed and must be reapplied for, with this only possible six months after leaving the countr

The visa will reportedly start in March and also allow holders to bring their spouses and families with them. To start using the visa, holders will also need to purchase private health insurance from their home country while taxes on any money one earns will also need to be paid through one's home country.

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