Lipid Nanoparticles Could Be Joining Chemical’s Hall of Fame

Every now and then, technologies come along in the chemical industry that really set it alight: the Haber-Bosch Process that gave the world synthetic fertiliser back in the early 1900s, or the accidental discovery of polythene.

One of the areas creating a buzz today is lipid nanoparticles, or LNPs. These complex fat compounds encapsulate and safely transport fragile mRNA molecules through the harsh environment of the body to their intended destination. Found in cosmetics and sunscreen, in some shape or form lipids have been around a short time already. But the latest LNP technologies shot to fame during the coronavirus. There’s murmurings they could be the technology of the millennium.

Unsurprisingly, a handful of chemical companies are embracing this nascent market with gusto. Like the early movers into EV battery materials, they want to be on the forefront at such a key moment when partnerships are up for grabs.

One such group is Evonik Industries AG. The Essen-based company’s historic roots read like a who’s who of German industrial icons: Röhm, Degussa, and Goldschmidt. But it’s pivoting away from legacy bulk chemicals based on fossil fuels to newer, cleaner and more complex playgrounds. It now counts Covid-19 vaccine maker BioNTech among its LNP customers.

Revolution can be a slow process in the safety-critical and conservative chemical industry. With mRNA rapidly showing the hallmarks of becoming a third class of drug, LNPs too have exploded onto the scene and there’s less time for chin scratching. That plays to the strengths of specialty chemical makers like Evonik with experience in drug delivery, according to Thomas Riermeier, head of Evonik’s Health-Care business.

“Covid-19 was a real game-changer. It was mRNA’s breakthrough from a technology point of view and LNPs are the established technology for delivery:” Riermeier.

In 2019, seven of the top 10 best-selling drugs were injectable biologics, the remainder traditional oral small molecules. But two years is a lifetime now.

With the onset of the pandemic, the supply of lipids became critical. It took drugmakers about a week to decode the coronavirus, and then it was up to Evonik and rivals like Croda and Merck to build up the capacity to provide the vaccine delivery systems. The setting up of a world-scale manufacturing plant — something that could normally take up to 2 years — got condensed into a couple of months at Evonik, according to Riermeier. Some other customer projects were put on the back burner to focus resources while management pulled in expertise from across the group and extended shifts into the weekend.

With a history in drug delivery dating back 65 years, Evonik saw LNPs as a natural progression. Its EUDRAGIT polymer excipient developed by Röhm back in the day opened up time-release oral drugs. Acquisitions followed over the years, taking Evonik into a new class of biodegradable polymer for injectable drugs, and providing expertise across formulation, clinical trials and manufacturing.

The breakthrough moment in LNPs for mRNA came when Evonik connected with Professor Pieter Cullis of the University of British Columbia, a godfather-type figure in the world of lipids after decades researching the subject of delivery systems for nucleic acid therapeutics. Emboldened by Cullis, Evonik acquired Transferra Nanosciences, a so-called contract development and manufacturing organisation focused on the biotech industry. It now had a full-service offering, right up to finished vials.

“We knew something was cooking and that it was very likely that vaccines would be the first application for mRNA,” Riermeier said. Looking into the future, “we know very well what’s coming up,” he added.

Interest in lipids is soaring. Whether it’s cancer treatments or precision bombing growth hormones to a vital organ of a child, a host of clinical trials are being unleashed. In what felt like an understatement, Riermeier confirmed Evonik’s level of enquiries is up “significantly.” And any plans to expand capacity to meet market growth remain under wraps for now.

There must something that could ruin the LNP party. On this, Riermeier has to pause. It’s been a pretty full-on year or so down at Evonik Health Care and he’s dredging the recesses of his mind to identify any blot on the landscape. Beyond the spectres of new Covid-19 variants or another altogether different pandemic, nothing really comes up.

There have been studies into whether LNPs could be toxic and cause organ damage, but Riermeier feels those concerns have been allayed by the sheer level of scrutiny on coronavirus vaccines. Besides the matter of safety is in the hands of a heavily-regulated drug industry, which is eagerly pouring money into mRNA. Sanofi alone is investing EU400 million in a specialised R&D hub.

mRNA is going mainstream and it seems to be a case of watch this space for lipids.

Riermeier is keeping a close eye on gene-editing. The CRISPR technology to target and edit DNA is gaining traction and increasingly complex carriers will be required to provide a stable environment for the delivery of protein complexes into cells and edited tissues to the brain and other vital organs.

There’s also work to do on the source of lipids themselves. Following the BSE outbreak in cattle and Creutzfeldt-Jakob Disease, some pharma companies still won’t have animal-based products in the vicinity of their manufacturing sites, let alone shuttling their mRNA through a patient. Often the starting block is a plant-derived lipid, which can then be synthetically enhanced, Riermeier said.

“Prior to Covid 19, you could almost have argued whether mRNA is going to stick around and whether it’s effective,” Riermeier said. “These doubts have gone.”

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