Speed or quality? When it comes to two-step chromatography purification, biopharmaceutical manufacturers want both, despite knowing, realistically, that each choice involves tradeoffs.
With purity, stability, toxicity, processing times, and costs hanging in the balance, the key optimization questions, therefore, are which purification efforts deliver the greatest return and how they can be combined to achieve the ultimate, optimal balance.
A small multinational team of researchers is among the first to address that question with an analytical model “to jointly manage speed-quality tradeoffs and stage-specific lead-time constraints in purification operations,” Yasemin Limon, PhD, assistant professor, Bilkent University, tells GEN. This method guides optimization decisions, helping biomanufacturers decide how aggressively to intervene at each purification step of a serial, two-step chromatographic purification process based upon the costs of the intervention and the time constraints of the purification steps.
The model, based on queueing network theory, captures what the authors call “practically relevant” tradeoffs, correlating intervention efforts, their effects on stability timeframes, and the probability of quality enhancement. It was developed by Limon and colleagues, Tugce Martagan, PhD, associate professor, Northeastern University, and Ananth Krishnamurthy, PhD, professor, Indian Institute of Management Bangalore.
“Understanding how much and at which stations interventions should be applied allows biomanufacturers to optimize system performance without compromising on manufacturing lead times,” the team reports. Thus, the risk of long wait times between steps that may cause product deterioration is reduced.
They divided purification optimization steps into two categories: Type I—those that improve batch quality without increasing purification processing time (such as selecting better resins or reagents)—and Type II—those that increase both batch purity and purification processing times (such as reducing flow rates).
For each category, they evaluated how each optimization affected stage-specific lead-time constraints and how those constraints varied between the two categories of interventions.
Choices are interrelated
“Optimal intervention efforts change with costs,” they acknowledge. Here are the key takeaways:
Under-investing in upstream purification pushes purification downstream, where increasing the polishing time may risk product stability
For Type I interventions, put maximum effort into the least expensive options until product stability becomes a constraint
For Type II interventions, each decision affects both quality and processing times. Characterize process times at each chromatography step and document stability-based time windows to create a reference chart that can be used repeatedly
Shortening the stability window for step two necessitates more aggressive purification at step one. Fresh time constraints—related to new molecular stability data, for example—should not be evaluated in isolation
Create a reference map for the range of operating conditions typically encountered in your facilities, along with possible interventions, their costs, and stability-based time effects. Use this as a real-time reference on the manufacturing floor
“The optimal policy depends on costs, processing times, and lead-time constraints,” Limon says. “Decisions at the first and second chromatography steps are interdependent.” Map those effects early to guide decisions in real time.
She recommends turning the model into a decision map. “A manufacturer can estimate its own process parameters (batch arrival rates, processing times at each purification step, stability-based time limits, intervention costs, and the effect of each intervention on quality and processing time) and use the model to identify which intervention policy is optimal under those conditions.
“Distinguish carefully between interventions that improve quality without increasing processing time and interventions that improve quality but slow the process,” Limon continues. “The first type affects lead time mainly through congestion at the downstream step, while the second type directly affects processing time and can make stage-specific lead-time constraints restrictive. Therefore, firms should quantify how interventions change processing time, congestion, and feasibility with respect to stability-based time windows.”
A new continuous bioprocessing platform for advanced therapy medicinal products (ATMPs) could help manufacturers increase yields and improve productivity, allowing them to treat larger groups of patients.
The platform, developed by an independent U.K. innovation center, the Cell and Gene Therapy (CGT) Catapult, aims to provide an additional option for manufacturing gene therapies.
“We’re not going to get rid of batch processing, but it is another tool for people to use when developing and manufacturing gene therapies and other ATMPs that could tackle some [existing] bottlenecks,” explains Bilal Ozdoganoglu, an associate senior scientist at the CGT Catapult.
Ozdoganoglu spoke at the Bioprocessing Summit Europe in March about the downstream capture and polishing step of the continuous bioprocessing platform earlier this year.
According to Ozdoganoglu, the platform aims to use continuous bioprocessing to overcome the problems of low yields and productivity, allowing ATMPs to cater to larger groups of patients while taking advantage of economies of scale.
The platform uses perfusion technology in the upstream, followed by, in the downstream, a clarification step and multi-column chromatography.
“Multi-column chromatography is almost bread and butter of more traditional biologics, but it’s relatively new in the gene therapy space,” he says.
“As such, we had quite a few challenges to overcome to allow a system originally built for mAbs to cater for gene therapies.”
For the polishing step, Ozdoganoglu explains that they heavily relied on digital modeling to generate parameters they could take into the laboratory.
According to Ozdoganoglu, the recovery rates and overall performance of the continuous system were slightly better than, or comparable to, traditional batch processing.
The next step, he explains, is to develop the platform further so it becomes an alternative to batch processing.
As such, he says, the CGT Catapult is looking for collaborators, including therapy developers as well as vendors, automation suppliers, and contract development and manufacturing organizations (CDMOs).
Bacterial expression systems are becoming more versatile, say Swedish contractor NorthX Biologics and Austrian technology firm enGenes Biotech, who have teamed up to create an integrated, E.coli-based protein production platform.
E.coli-based protein expression systems are not a new idea. They have been around since the 1970s and used to make everything from recombinant human insulin to treatments for growth hormone deficiency.
They are generally cheaper than expression systems that use mammalian cells, primarily due to lower reagent costs. They also tend to be faster to set up, easier to scale, and have a reduced risk of viral contamination.
Typically, E.coli-based systems are selected for the manufacture of simple proteins that do not require human-like post-translational modifications such as glycosylation. However, recent advances in strain engineering are starting to expand their scope.
As a result, more biopharmaceutical firms are considering them for commercial-scale protein production, says Ola Tuvesson, CTO at NorthX, who cites this demand as a driver for the enGenes partnership.
“The biggest growth vectors are biosimilar manufacturing, peptide therapeutics, and antibody fragments, including ADC components. Advances in glycosylation engineering are also expanding what the platform can address at the higher end of biologics complexity.
“Several trends are reinforcing this direction: sustained pricing pressure pushing biopharma away from higher-cost production systems for this segment of the pipeline, growing investment in CRISPR-based strain engineering that extends microbial platforms into more complex program types, and a manufacturing infrastructure that needs to keep pace with industry demand,” Tuvesson tells GEN.
Integrated pathway
NorthX Biologics and enGenes’ strategy is to offer an integrated service that covers everything from strain design through manufacture.
Tuvesson says, “The E. coli development to GMP manufacturing pathway typically covers expression system development, process development, scale-up, and transfer into GMP production. While the technical steps are well established, the challenge in many programs is that these stages are often handled by different providers, leading to delays, rework, and increased scale-up risk.
“The pathway we are establishing addresses this fragmentation by integrating expression development and GMP manufacturing into a single, aligned workflow. This reduces handovers, improves data continuity, and helps ensure that the expression system is optimized from the start for manufacturing at scale,” he adds.
The new pathway will combine high-throughput screening platforms, multi‑fermenter systems, and multivariate experimental design with advanced analytical support and scale-up engineering.
According to NorthX Biologics and enGenes Biotech, the idea is to enable rapid iteration and the generation of decision-grade data early in development, supporting more robust and scalable processes.
There is an option to extend the partnership, according to Tuvesson, who says, “The collaboration may also open up opportunities to implement more continuous manufacturing approaches over time.”
The firms plan to monetize the platform by providing it to biopharma customers as a manufacturing service, rather than out-licensing, as Tuvesson explains.
“Expression systems and processes developed for a specific protein can be transferred under standard commercial terms. However, the pathway itself is not a standalone licensable product.
“The focus is instead on integrating expression development and manufacturing into a single workflow, reducing handovers and enabling faster development timelines,” he says.
In addition to making products, a bioprocessor should be thinking more about solvents. “Solvent recovery is becoming a critical part of operational resilience and fiscal strategy for bioprocessing companies,” says Rudy Morin, engineering and modular solutions manager at Koch Modular. “It provides three primary benefits: operating expense reductions, supply-chain independence, and corporate sustainability.”
The financial case is especially compelling for bioprocessors that rely on high-purity HPLC- or USP-grade solvents, which are costly to procure and expensive to dispose of properly. By recovering and reusing solvents from waste streams, companies can meaningfully cut virgin-solvent purchases while reducing hazardous waste disposal costs. Morin notes that the economics tend to work in a bioprocessor’s favor. “The payback periods are often attractive given quantities and solvent costs, and the recovery system quickly becomes a predictable long-term asset,” he says.
Supply-chain reliability has become an equally pressing concern. Geopolitical tensions, severe weather, and transportation disruptions have laid bare the vulnerabilities in chemical sourcing. Solvent recovery addresses this by creating a closed-loop supply within the facility itself. “A solvent-recovery system gives bioprocessing facilities total control over their solvent supply and business continuity,” Morin says.
Implementation, however, is rarely straightforward. Bioprocessing waste streams typically contain multiple solvents, water, and solids. Such mixtures often demand sophisticated separation technologies, such as pressure-swing distillation, extractive distillation, vacuum distillation, or liquid-liquid extraction. “Each additional unit operation adds intricate controls and operational variables, making the initial design phase absolutely critical,” Morin says.
Capital costs present another barrier. Automated systems generally start in the low seven-figure range, with complexity driving costs higher. To manage risk, Morin recommends combining pilot testing, process simulation, and modular construction. Pilot testing clarifies feed characteristics and yields critical process data; simulation software optimizes designs before a dollar is spent on construction; and modular fabrication reduces project risk by moving work off-site, compressing schedules, and tightening quality control.
Looking ahead, Morin sees meaningful opportunities in advanced extraction technologies and modular deployment. Liquid-liquid extraction, for instance, can recover products directly from fermentation broths while enabling downstream solvent recycling. For facilities considering the leap, his advice is practical: start with a clear design basis, conduct a rigorous economic analysis, and engage experienced process-engineering partners early. “Any solvent-recovery stream is worth a conversation with an experienced process engineering company, given the multiple potential benefits,” he says.
As cost pressures and sustainability commitments converge, solvent recovery is increasingly positioned not as a compliance measure but as a strategic investment—one capable of delivering measurable value across operations, supply chains, and environmental performance.
In preclinical models, the administration of KPT-330 (selinexor) prevented export of R-loops and led to significant improvement in inflammation, liver damage, fat gain, muscle loss and overall lifespan.
“Chronic, widespread inflammation is a driving factor in many age-related diseases, including cancer, and our research has discovered one reason why this happens,” said Rugang Zhang, PhD, professor and chair of Experimental Therapeutics at UT MD Anderson and corresponding author on the study. “Understanding the cause is the first step toward developing treatments. We saw encouraging results using a drug that has already been tested in humans, paving the way for potential clinical use to alleviate age-related conditions.”
Cells begin releasing signals that contribute to chronic inflammation once they enter senescence and stop dividing. Researchers have now pinpointed R-loops as a key component to modulating these inflammatory signals.
An R-loop is a temporary cellular structure created during transcription, when a double strand of RNA and DNA becomes tangled with a third displaced single strand of DNA. While R-loops are traditionally confined to the cell nucleus, the study found that cells in senescence increasingly export R-loops into the cytoplasm. These R-loops attach to fragments of DNA debris to trigger chronic inflammation.
This study identified the two proteins involved in exporting R-loops, DDX1 and XPO1. DDX1 attaches to the R-loop inside the nucleus to facilitate export. XPO1 allows the R-loops to be transported into the cytoplasm by forming a complex with DDX1.
Researchers administered KPT-330, a FDA-approved drug for treating multiple myeloma that blocks nuclear export. The R-loops remain trapped inside the nucleus and could not trigger an inflammatory response.
The study showed that shutting down nuclear export by blocking XPO1 in preclinical mouse models suppressed inflammaging, reduced liver fibrosis, lowered systemic inflammatory markers, and reversed age-related body composition changes.
In a separate experiment, the same inflammatory alarm enabled the immune system to find and eliminate precancerous cells. The authors state that future studies could explore blocking DDX1 specifically, instead of shutting down all nuclear export, to mitigate side effects.
Jonathan D. Grinstein, PhD, North American Editor of Inside Precision Medicine, hosts a new series called Behind the Breakthroughs that features the people shaping the future of medicine. With each episode, Jonathan gives listeners access to his guests’ motivational tales and visions for this emerging, game-changing field.
Philippe Pouletty, MD, is one of Europe’s most accomplished life sciences entrepreneurs, with a track record of creating category-leading companies in both biotechnology and medical technology. Over more than three decades, he has repeatedly identified breakthrough scientific innovations, assembled world-class teams, and scaled businesses from inception to global prominence.
His most celebrated success is Abivax, the biotechnology company he founded and led as chairman for a decade. Under his leadership, Abivax evolved into a global biotechnology powerhouse, achieving an approximately $10 billion market capitalization after positive Phase III results in 2025. In 2025, the company delivered the strongest stock market performance of any European company across all sectors.
Philippe Pouletty, MD, Co-founder and CEO of Truffle Capital and Co-founder of Abivax and Carvolix. [Truffle Capital]
Today, Philippe Pouletty is applying the same entrepreneurial playbook to Carvolix, a next-generation cardiovascular MedTech company focused on heart valve disease and stroke. Carvolix is built on the strategic combination of breakthrough implant technologies, AI-powered software, and autonomous mini-robotics. The vision follows the successful Abivax model: bring together differentiated technologies, speed up industrialization, build clinical leadership, and create a company that can transform patient outcomes while attracting significant strategic and public-market value.
A physician, scientist, inventor, and venture capitalist, Philippe has founded or co-founded numerous successful life sciences companies and holds dozens of patents, including one of Stanford University’s highest-revenue-generating life sciences inventions. With Abivax and now Carvolix, he has demonstrated a rare ability to build transformative healthcare companies that combine scientific innovation, commercial scale, and lasting impact for patients worldwide.
This interview has been edited for length and clarity.
IPM: Having spent time in both Silicon Valley and Europe, what cultural or structural differences have you discovered that have given Europe an advantage in deep tech and life sciences or that may be holding it back when compared to companies in the United States?
Pouletty: In California, financial resources are virtually limitless as long as you have a company with a great mission that addresses large medical needs and markets. Unfortunately, Europe is behind. France is an excellent place to begin, with companies to hire, good engineers, management, and so on. However, raising more than €50 or €60 million is often difficult when compared to the United States. So, things have improved over the last two decades, and there are some good grants and tax breaks available to help businesses raise capital.
However, the stock market in France and Europe is not as competitive as the Nasdaq. So, while I love the United States, many French and European companies must list on Nasdaq in order to grow, remain independent, and eventually reach the commercial stage. Then it becomes an American company, often a large pharmaceutical company or one with significant innovation. Wonderful small company. Let us buy it. So that’s great for the United States and big pharmaceutical companies. However, Europe’s prospects for the next 20 years do not look promising. The challenge for Europe is that competition will primarily come from the United States, China, and, most likely, India.
Europe faces a difficult task in catching up. But, because I’m still a crazy entrepreneur who is interested in European policies, it’s time for France and Europe to do the right thing and establish independent companies. I believe what is of interest is to do things that have an impact on patients. And if you have a positive impact on patients, you will increase shareholder value; however, you should not always focus on doing an IPO or selling the company as soon as possible. What matters is developing completely novel, radical innovation that will change or prolong the lives of patients while also benefiting the environment.
IPM: As one of Europe’s standout biotech success stories, what set Abivax apart from the many biotech companies that never scale beyond promising science in Europe before venturing out west?
Pouletty: What we like to do at Abivax and Carvolix is build businesses by merging two or three of our biotech companies when much of the R&D is completed in order to reach critical mass and have several product candidates available. So if one fails, the company is not doomed. To be able to attract extremely experienced management. There are too many very small businesses in Europe. For example, the president, Emmanuel Macron, likes to refer to France as the “startup nation.” The goal should not be to become the startup nation. The goal should be to develop world leaders similar to those in the United States, regardless of sector.
Abivax emerged in 2013. Three of our biotech companies were able to complete a Euronext IPO, which remains the largest biotech IPO on Euronext. We had raised €58 million at the time. Surprisingly, the most advanced product candidate, a drug candidate, failed following the IPO in phase two. So it was unpleasant but not disastrous because the second product candidate, which was only in phase one at the time, is now assembled, has a $7 to $10 billion valuation, and has had excellent results in phase three in treating ulcerative colitis patients.
So, it appears to be a straightforward business plan. It’s not correct. You must stay focused on your mission. Disappointment can occur during pre-clinical R&D and clinical development. Of course, this happens to the majority of biotech companies. And this is why, for example, when sailing across the Atlantic or Pacific, you must keep in mind that reaching the other side requires a strong team; sometimes we change the team and the CEO.
But we are very proud to say that the above acts would not exist without Truffle Capital, and I was chairman of the board for ten years and was very pleased. it looks like the drug should be approved. In the last few days the stock dropped because the long-term maintenance clinical results showed great efficacy and there were very few cancers, which is typical in this kind of patient population with a dysfunctional immune system.
So to me, it’s a little hiccup, but I’m very confident it will change and improve the lives of the patients with ulcerative colitis. Now, maybe the little drop in valuation will boost the M&A appetite of some big pharma companies. And I can send that because, well, not any more shareholders are involved in the epilogue. It’s my personal opinion, of course, about the future. I could be wrong.
IPM: How do emerging European companies like Carvolix or Abivax compete with American or Chinese companies? Do you try to establish a market in Europe first, then expand internationally, or do you try to do everything at once? What’s your strategy there?
Pouletty: When Carvolix first launched in the United States, the largest market was heart valve software. So, while launching in the United States with a very concentrated focus team, step by step with specialized centers and then with the market, research based on this successful launch will expand. We may later hire a partner for the United States, or agents or a single partner.
We want our products to be agnostic, regardless of whether the valve is Abivax, Medtronic, or Abbott, so that hospital clinicians can choose which valve system to use for their patients with our software and robot. We will continue to conduct direct sales in Europe, as we have in the past. If you have a highly innovative product, you will need a small, highly technical sales force that can visit clinics, hospitals, and clinicians to be successful in Asia.
IPM: How do you get clinicians and hospitals to buy into something like this, which isn’t really an upgrade of their system, but rather the introduction of a whole new line?
Pouletty: At first, we assumed that top-tier cardiologists who treat hundreds or thousands of patients would not require our services. And it will primarily benefit younger, less-trained cardiologists. However, we conducted studies in France with data from the world’s leading cardiologist for aortic valve replacement, as well as in Australia with highly trained cardiologists. They said, “That’s great because I’m less stressed during the implantation.” I may not need a second cardiologist in the room, as is frequently required, and I may see more patients during the day.
It’s somewhat similar to cars. You could argue that autonomous cars will not meet the needs of taxi drivers. But yes, taxi drivers will say, “Great.” I can drive more miles, transport more passengers, and feel more relaxed at the end of the day. I have no doubt that it will become the norm in medium and small hospitals over the next few years. Place special patients in the care of an expert cardiologist. Now for given special patients in the hands of an expert cardiologist, we don’t pretend it will do better. But many more patients who have not the chance, whether it’s hardware replacement or brain stroke treatment to healthcare… will if we are successful.
It is critical to ensure that introducing AI and robotics does not prolong the procedure. It takes roughly the same amount of time or appears to be shorter. However, it is always under clinical supervision. We can take over and stop the procedure, just like on a plane, and carry it out manually. However, after some initial training with a few patients, the clinician will most likely allow the procedure to be completed autonomously while closely monitoring the screen to ensure that everything is running smoothly.
IPM: How do European healthcare systems differ in their ability to adopt new biotech and medtech innovations?
Pouletty: No system is perfect. I do a very simple comparison in France and Europe. even patients who do not work will be treated in the hospital at no cost. In the U.S., you’d better have a plan. You’re working in the company to be covered. There is no perfect system. Certainly, pricing of drugs and medical devices in the U.S. is higher, which means that there is an incentive for investors and companies to do high-cost R&D to recoup their investment through high pricing. In France and Europe, there is a tendency to have to push for low pricing and low reimbursement, which is why for oncology drugs more are available and reimbursed in the U.S. today than for non-college products.
But there is not enough emphasis on the long-term impact of innovation. And pioneers often looked at the shorter impact and said, oh, that’s two weeks, let’s say. I’ll give you one example. In oncology, pancreatic cancer is tough because the diagnosis is very often very late when you have big tumors.
It’s very clear that if it were up to me, we would do imaging every two years. We would catch very small, tiny tumors very early on because an anatomical change in our cells within two years could indicate that you need to go and see if you should remove this little tiny one. But that’s not common in practice because it would be expensive to do an MRI every two years on everyone after 50 years old.
So beyond drugs and medical devices and the practice of medicine, how do you do? Preventative medicine needs to be greatly improved, and governments are not very good at looking at these approaches to improve healthcare. So, I went into politics. I would turn on that. I decided 25 years ago I would not run for any elected office and focus more on starting companies.
This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.
Hacking the atmosphere: geoengineering gets a reality check
Solar geoengineering, the controversial idea that we could deliberately intervene in the climate system to counteract global warming, is moving beyond computer simulations and into the practical engineering challenges required to make it real.
Researchers are now working on aircraft, materials, and other systems for solar geoengineering. But as they delve into these details, they’re finding that even early deployment would require significant new infrastructure, time, and investment.
MIT Technology Review Narrated: inside interoception, the hidden sense of how you feel inside
Scientists have a word for how we sense ourselves from the inside: interoception. Today, thanks to a 2021 Nobel Prize and new tools that can map internal signaling across the body, research into interoception is taking off.
This is our latest story to be turned into an MIT Technology Review Narrated podcast, which we publish each week on Spotify and Apple Podcasts. Just navigate to MIT Technology Review Narrated on either platform, and follow us to get all our new content as it’s released.
The must-reads
I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.
1 SpaceX is now valued higher than Amazon Its market value hit $2.659 trillion yesterday. (Axios) + A post-IPO stock surge also briefly pushed it above Microsoft’s. (Quartz) + It’s now the world’s fifth most valuable company. (Guardian) + SpaceX is acquiring AI coding startup Cursor for $60 billion. (CNBC)
2 G7 leaders want access to top US AI models They’re pushing to escape restrictions on the likes of Fable 5. (Reuters $) + The Mythos shutdown has sparked a global scramble for sovereign AI. (Fortune) + The world is looking to ditch US AI models. (MIT Technology Review)
3 Trump’s AI export strategy has run into Trump’s export controls His administration risks undermining its own AI plans. (Axios) + It now effectively has a licensing regime for frontier AI. (Fortune) + Here’s how a top Chinese AI model overcame US sanctions. (MIT Technology Review)
4 Huawei’s big comeback has exposed the limits of US chip controls It’s overcome restrictions on advanced chipmaking gear. (Financial Times $) + The AI boom has ignited Asia’s chip companies. (NYT $)
5 AI fears are pushing Silicon Valley toward gene-editing startups They want smarter babies to counter superintelligent AI. (Mother Jones) + The pursuit of perfect babies is an ethical mess.(MIT Technology Review)
6 A brain implant has enabled a speechless ALS patient to work full-time The system translates his brain activity into speech. (The Register) + He’s become the first “power user” of a BCI. (MIT Technology Review)
7 A leak has revealed details of Peter Thiel’s secret society Its program ranges from cult-building to prepping for World War III. (Wired $)
8 ChatGPT’s market share has slipped below 50% for the first time Thanks to the rise of Gemini and Claude. (TechCrunch)
9 A quantum state that lasts forever may finally be within our grasp Experiments suggest that quantum “eternity” is possible. (New Scientist $)
10 Commodore has made a digital detox phone that isn’t dumb The Callback combines gadget nostalgia with modern needs. (The Verge)
Quote of the day
“The Entity List is like whack-a-mole and you’ve got to keep whacking the moles.”
—Philip Luck, who studies global supply chains at the Center for Strategic and International Studies, tells Reuters that a lack of new blacklistings is likely leading American innovations to adversaries who could use them against the US.
One More Thing
COURTESY OF DEEPMIND
This is the reason Demis Hassabis started DeepMind
Watching DeepMind’s AI master the ancient board game Go, Demis Hassabis realized that his company was ready to take on one of the most important and complicated puzzles in biology: predicting the structure of proteins.
The result was AlphaFold2, an AI that could predict the shape of proteins down to the nearest atom. “It’s the most complex thing we’ve ever done,” Hassabis told MIT Technology Review.
Taking on scientific problems is the culmination of what Hassabis set out to achieve, and it’s what he wants to be known for. “This is the reason I started DeepMind,” he says. “In fact, it’s why I’ve worked my whole career in AI.”
A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)
+ This mesmerising footage of wind rolling through grass looks like CGI. + The glorious early days of internet discovery have been revived by the return of StumbleUpon. + A German subway entrance has been delightfully designed as an old tram car crashing into the pavement. + The Last Museum lets you search across 5.8 million museum artworks spanning from 3000 BC to the present day.
UniQure will submit a marketing application in the third quarter seeking accelerated approval for the treatment, called AMT-130. The decision comes after a recent meeting with FDA officials during which the agency agreed that a three-year analysis of an early-stage study that showed a benefit for patients with Huntington’s was “acceptable” to support a marketing application, the company said.
These are the same AMT-130 data that former FDA officials, most notably Commissioner Marty Makary and Vinay Prasad, the agency’s top regulator of cell and gene therapies, previously concluded were insufficient to support a marketing application.
Should the federal government try to slow — or even block — U.S. biotech deals that could benefit China?
The question of what, if anything, the U.S. should do about the growing strength of the Chinese biotech industry has reached a new intensity in recent months. A handful of legislators are pushing to add biotechnology to the list of industries covered by the COINS Act, which allows the U.S. government to restrict investments in certain cases. That would enable federal scrutiny of licensing deals, equity investments, and other arrangements that are becoming evermore prevalent in the biotech industry.
Venture capitalist Julie Grant feels that would be shortsighted, a misguided effort to try to turn back time on an interdependency between U.S. and Chinese industries that’s been growing for decades. Even if it were feasible to cut off American companies’ reliance on Chinese research organizations and drug developers, she believes doing so would actually hamper U.S. drug development and hurt patients.
Merck & Co. will partner with Protillion Biosciences to discover multiple new therapy candidates through a collaboration that could generate up to $510 million in milestone payments for the artificial intelligence-based drug design company whose “lab-in-the-loop” approach combines AI with a continuous feedback loop of experimental wet-lab data.
The collaboration, launched through a multi-target discovery collaboration and license agreement, is designed to combine Merck’s global expertise in discovering novel therapeutics with Protillion’s Prot-MaP on-chip antibody discovery platform.
Prot-MaP, short for Protein Display on a Massively Parallel Array, is designed to facilitate AI-based optimization of therapeutic antibodies through the quantitative analysis of protein libraries with unprecedented speed, scale, and precision, characterizing millions of variants per run and avoiding the common pitfalls of model overfitting.
The result, according to Protillion, is the identification of optimized biologics with sophisticated therapeutic profiles such as pH-dependent sweeping and multi-target specificity—profiles that are difficult to achieve with traditional methods.
Protillion says Prot-MaP is intended to enable the engineering of novel biologics by generating megascale, just-in-time quantitative antibody binding datasets for protein design AI. The platform enables the generation of tens of millions of clusters of immobilized proteins directly on an Illumina DNA sequencing flow cell through efficient tethered in situ transcription and translation.
Prot-MaP was invented by the company’s CEO and co-founder, Curtis Layton, and co-founder Will Greenleaf, PhD, a professor of genetics at Stanford University School of Medicine and a member of Protillion’s Scientific Advisory Board. After receiving his PhD in computational biology from Duke University, Layton studied with Greenleaf as a postdoctoral fellow in the genetics department at Stanford Medicine.
Curtis Layton, PhD, CEO and co-founder of Protillion Biosciences
Layton developed Prot-MaP while working in Greenleaf’s lab, then organized Protillion in 2019 to commercialize the technology. Layton’s work pioneered a new approach to high-throughput interrogation of biochemical systems, tackling ultra-high-impact technology approaches for drug discovery by uniting fields that included protein engineering, next-generation sequencing technology, molecular biology, in vitro transcription and translation, computational biology, software development, and various engineering disciplines.
Days rather than months
“Prot-MaP is a technology platform that allows us to test millions of protein interactions simultaneously, generating an unprecedented amount of data in a matter of days rather than months. For example, we can rapidly evaluate large libraries of therapeutic protein candidates to see how they bind to different targets and how they behave under different biological conditions,” Robert Hollingsworth, PhD, Protillion’s CSO, told GEN.
“We then combine that data with proprietary AI and machine learning tools to understand what drives the best-performing proteins and quickly design improved candidates. This gives us the ability to engineer antibodies with highly specific characteristics, such as stronger and more precise target binding, the ability to engage multiple targets, or the ability to activate only under certain physiological conditions,” Hollingsworth explained. “In practical terms, Prot-MaP helps us discover and optimize better drug candidates faster, with a level of insight and precision that has not previously been possible at this scale.”
Prot-MaP allows Protillion to test up to one million protein variants simultaneously in a single experiment and generate results in as little as 48 hours.
“Because we operate multiple proprietary platforms in parallel, we can rapidly scale that capability and generate enormous amounts of experimental data on demand,” Hollingsworth explained.
What makes Prot-MaP unique, he continued, is not just its scale, but its combination of scale, speed, and AI.
Robert Hollingsworth, PhD, Protillion Biosciences’ CSO
“The platform is designed to seamlessly connect high-throughput protein testing with proprietary machine learning models, allowing us to quickly identify promising drug candidates, understand what makes them work, and design improved versions,” Hollingsworth said. “This enables us to tackle everything from discovering entirely new therapeutic molecules to optimizing existing candidates for multiple desired characteristics. In practical terms, Prot-MaP helps us find and develop better biologic medicines faster and more efficiently than traditional approaches.
Opposite approach
How does Prot-MaP overcome the complexity of protein molecules, which has long been a hurdle in protein and biologics design?
“Many companies start with AI and then look for data. We took the opposite approach,” Hollingsworth said.
Rather than relying primarily on computer predictions of protein structure, he elaborated, Protillion can apply Prot-MaP to directly generate large-scale functional data and identify the best therapeutic candidates based on real-world experimental results.
“What makes this especially powerful is the sheer scale of the data we can generate. While much of the industry has focused on applying AI to relatively limited biological datasets, we believe that the biggest challenge in drug discovery is obtaining enough high-quality data to truly understand the complexity of protein function. Prot-MaP was built to solve that problem,” Hollingsworth said.
By generating millions of protein measurements in parallel, Protillion says, it can create the kind of rich, large-scale datasets needed to train more powerful and predictive machine learning models. Those models, in turn, help design and optimize better therapeutic candidates faster and with greater precision.
“Prot-MaP combines high-throughput experimentation with AI. The platform allows us to rapidly generate the data, and the AI helps us learn from it—creating a cycle that accelerates the discovery of next-generation biologic medicines,” Hollingsworth said.
Speaking with GEN, Layton said Protillion and Merck have charted a course for the start of their drug discovery collaboration.
“Our first two programs focus on inflammatory diseases, where we see significant unmet medical need and strong opportunities for differentiation,” he said.
Immune-mediated inflammatory disorders are Merck’s specialty within its therapeutic area of focus in immunology. Merck focuses on several other therapeutic areas, which include oncology, vaccines, infectious diseases, cardiometabolic and respiratory diseases, neuroscience, and ophthalmology.
“However, the Prot-MaP platform’s capabilities extend far beyond inflammation, enabling the discovery and development of novel biologics across a broad range of therapeutic areas,” Layton added. “As we continue to advance the platform, we expect to expand into additional disease areas where its unique capabilities can have the greatest impact.”
Tech-focused pipeline collaborations
Merck has launched several tech-focused pipeline collaborations in recent months aimed at replenishing its cancer and immunology pipelines, with the goal of developing new therapies that can recoup the billions of dollars in sales the pharma giant will lose as patent exclusivity expires in the United States and elsewhere for its aging blockbusters, including cancer immunotherapy Keytruda® (pembrolizumab) and Gardasil® 9 (Human Papillomavirus 9-valent Vaccine, Recombinant).
In March, Merck inked an up-to-$2.2 billion collaboration with Quotient Therapeutics to apply Quotient’s somatic genomics platform to discover novel drug targets in inflammatory bowel disease (IBD). Also that month, Merck launched a partnership with Infinimmune to apply its Anthrobody® discovery platform and GLIMPSE antibody language model to identify and develop antibody candidates against multiple undisclosed Merck-designated targets. Merck agreed to pay Infinimmune an undisclosed upfront payment and up to $838 million in milestone payments.
Merck has also launched several tech-focused partnerships, with partners that include:
Google Cloud—An up-to-$1 billion collaboration announced in April to deploy an agentic platform across Merck’s R&D, manufacturing, commercial, and corporate functions. Google Cloud engineers are working alongside Merck teams to deploy Google Cloud’s most sophisticated AI, including Gemini Enterprise.
Tempus AI—An expanded, multi-year collaboration of undisclosed value announced in March, aimed at accelerating discovery and development of precision medicine biomarkers, and supporting Merck’s oncology and potentially broader therapeutic portfolios.
Mayo Clinic—An R&D agreement of undisclosed value to apply AI, advanced analytics, and multimodal clinical data to support drug discovery and development. The agreement integrates Mayo Clinic’s Platform architecture, as well as clinical and genomic datasets, with Merck’s ambition of harnessing AI-enabled virtual cell technologies to enhance disease understanding, improve target identification, and drive early development decisions.
In its latest collaboration, Merck has agreed to pay Protillion an undisclosed upfront payment, plus up to $510 million in payments tied to achieving research, development, and commercial milestones toward the successful development of an unspecified number of therapies.
“Compelling opportunity”
“Powerful emerging technologies offer the potential to transform the speed and precision with which we characterize protein landscapes and identify novel therapeutic candidates,” Juan Alvarez, PhD, vice president, discovery biologics at Merck Research Laboratories, said in a statement. “Protillion’s platform offers a compelling opportunity, and we look forward to working with the team to advance these programs.”
Illumina’s venture capital arm, Illumina Ventures, is among investors in Protillion, having joined ARCH Venture Partners in 2022 to co-lead an $18 million financing in 2022.
Based in Carlsbad, CA, Protillion has grown rapidly to a workforce of 30 people. In March, Protillion hired Robert Hollingsworth, PhD, a drug development executive with more than 30 years’ experience in biopharma, as CSO through a placement by executive search firm CollectiveMinds. Before joining Protillion, Hollingsworth was CSO at Shoreline Therapeutics, and earlier held positions in companies that included Pfizer (as vp and CSO of cancer vaccines and immunotherapeutics), Pharmacia & Upjohn (since absorbed into Pfizer), GlaxoSmithKline (GSK), and MedImmune (acquired by AstraZeneca).
Protillion says it is continuing to expand its team and facilities, with the aim of supporting its internal pipeline and high-value strategic partnerships.
“We plan to hire six more FTEs [full-time equivalents] by the end of the year,” Layton said.
on-chip antibody discovery platform.
