Feliza Mirasol is the science editor for 

Feliza Mirasol

On Dec 11, 2024, Intertek, a total quality assurance provider, announced that it entered into a partnership with CrystecPharma, a UK-headquartered crystal and particle engineering company that applies proprietary modified supercritical fluid (SCF) technologies to improve drug performance. The collaboration will aim to advance formulation science and accelerate development timelines for inhaled medicines, particularly dry powder inhaler (DPI) products.

Under the agreement, the companies will develop a “fast to clinic” platform that supports pharmaceutical clients by providing rapid DPI development—from the initial formulation concept to good manufacturing practice (GMP) clinical manufacturing. The companies are aiming to accelerate DPI development to less than half the time typically required. The agile, rapid framework will be designed to allow clients, who are looking to formulate small or large (biologics) molecules, or who are looking to repurpose existing APIs, to benefit from technology that enables crystallization of new forms of molecules. Clients will also have access to technology that allows for the manufacture of novel particles in ways that significantly enhance those particles’ therapeutic performance, according to a company press release.

“Combining the proprietary mSAS [modified supercritical anti-solvent] technology and the speed of early development that partnering with CrystecPharma affords, with the GMP manufacturing and analytics expertise at Intertek, provides the market with an unparalleled service in this area. This unique platform will enable highly effective, stable, and safe DPI medicines to be developed and brought to market in a fraction of the time previously possible,” said Chris Vernall, commercial director, Intertek, in the press release (1).

CrystecPharma’s proprietary drug formulation technology, mSAS, aims to improve the performance of therapeutics by using a supercritical fluid—typically carbon dioxide because of its low critical point conditions and attractive physical properties—to remove solvent rapidly from a drug solution. This rapid solvent removal allows the drug to precipitate as dry particles. SAS has many advantages, particularly its ability to crystallize drug molecules and remove solvent in a way that only parts per million is left behind in the final product. However, conventional approaches to using SAS have limitations. For instance, these processes are often unstable, difficult to scale, and the nozzles used are prone to blockage, according to CrystecPharma (2).

CrystecPharma’s technique allows many molecules that are traditionally challenging to formulate as powders to be developed in that format. The company also has a unique set-up that enables formulation and process development to occur in a matter of weeks, according to the company press release (1).

“The strength of our award-winning mSAS technology and Intertek’s expertise in analytical development and GMP clinical manufacturing creates unique opportunities to develop innovative, high-performing medicines and improved treatments for patients,” said Paul Thorning, co-founder and CEO of CrystecPharma, in the release (1).

The platform that Intertek and CrystecPharma are collaborating on will be made available starting in January 2025.

DPIs were initially developed for treating asthma and chronic obstructive pulmonary disease by delivering the therapeutic directly to the lungs. This direct-to-tissue delivery enables rapid action and lower doses than more conventional oral administration. In addition to other respiratory diseases, researchers are now exploring DPIs for other applications, including treatment of bacterial lung infections, delivery of vaccines, and systemic drugs such as insulin.

1. Intertek. Intertek Partners with CrystecPharma to Advance Formulation Science and Accelerate Development Timelines for Dry Powder Inhaler Products. Press Release. Dec. 11, 2024.
2. CrystecPharma. mSAS Technology. 

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The partners will aim to establish a platform that enables rapid development of DPI products.

Intertek Teams Up with CrystecPharma on Formulation and Development of Dry Powder Inhaler Products

In December 2024, GSK entered into strategic deals with two companies with the goal of advancing drug development. GSK and Relation, a UK-based platform biotechnology company developing medicines for diseases with significant unmet need, formed two multi-program collaborations focusing on the identification and validation of novel therapeutic targets for fibrotic diseases and osteoarthritis. In a separate collaboration, GSK and Muna Therapeutics, a Denmark-based biotechnology company focused on developing innovative therapeutics for neurodegenerative diseases, will identify and validate novel drug targets for the treatment of Alzheimer’s disease.

Under the two collaboration agreements with Relation, GSK will pay a total upfront payment of $45 million, comprising an equity investment of $15 million, according to a Dec. 10, 2024 press release (1). Relation will be eligible to receive success-based collaboration payments of up to $63 million. It will also be eligible to receive potential preclinical, development, commercial, and sales milestone payments averaging $200 million per target across both deals as well as tiered royalties on net sales of products.

Fibrotic diseases and osteoarthritis are debilitating diseases that affect millions of patients worldwide. They represent areas of significant unmet medical need, according to Relation’s press release.

“These diseases have few treatments that address their root causes. By combining Relation’s patient-centric discovery platform with GSK’s global scale and expertise, we have the potential to accelerate the development of transformative medicines for patients who have long awaited new therapies,” said David Roblin, CEO of Relation, in the release (1). “Our approach of generating data directly from patient tissue allows us to build a comprehensive picture of the underlying human disease biology at scale. This, combined with our deployment of machine learning, enables us to make unprecedented inferences about how to effectively intervene in disease processes.”

In the collaboration with GSK, Relation will lead observational studies with the aim of generating two unique functional disease data sets. Meanwhile, Relation’s Lab-in-the-Loop platform will be used to analyze these data by integrating human genetics, single-cell multi-omics directly from human tissue, functional assays, and machine learning to discover novel disease targets. The company stated in its release that this approach minimizes the risk of clinical failure by ensuring that targets are robustly validated before entering the clinic. Relation will apply its platform to a number of related fibrotic conditions as well as osteoarthritis. GSK will have worldwide development and commercialization rights to any targets resulting from Relation’s studies.

“Working with Relation enables us to gain deep and precise insights into human causal biology and apply these to therapeutic discovery through a data-driven approach, supported by Relation’s proprietary platform,” said Kaivan Khavandi, senior vice-president, global head of Respiratory/Immunology R&D at GSK, in Relation’s press release (1). “The resulting targets will be supported by robust translational packages, which will in turn provide clarity on deployment in early clinical evaluation, ultimately supporting our broader portfolio ambition to develop new medicines for fibrotic diseases and osteoarthritis—where there remains significant unmet medical need.”

Under the deal with Muna Therapeutics, GSK will pay €33.5 million (US$35 million) upfront, and Muna will be eligible to receive up to €140 million (US$147 million) per target in milestone payments, according to a Dec. 5, 2024 press release (2). Muna will also be eligible to receive tiered royalties on net sales of products. GSK and Muna will explore insights from Muna’s MiND-MAP platform, a technology that applies spatial transcriptomics to brain samples from Alzheimer’s disease patients, cognitively resilient individuals, healthy controls, and centenarians with and without cognitive impairment. The platform generates a unique dataset of significant breadth and resolution that is expected to drive the discovery and development of innovative medicines for Alzheimer's disease, Muna stated in its company press release (2). GSK, in return, will lead drug development and take responsibility for preclinical activities, clinical development, manufacturing, and commercialization.

This collaboration leverages Muna’s expertise in mapping the brain’s response to pathological protein aggregates and the company’s all-in-human platform that identifies cellular mechanisms, gene networks, and molecular interactions underlying brain resilience. Any resulting candidate drug targets will be validated using Muna’s suite of humanized cell and animal models, which are supported by insights from patient tissue and biofluid samples.

“Our agreement marks a pivotal moment in Muna’s evolution and in the broader Alzheimer's research landscape. By combining GSK's commitment to breakthrough science with our MiND-MAP platform's ability to deliver novel insights into brain resilience, we aim to transform the landscape of drug discovery for neurodegenerative diseases and bring new hope to millions of patients worldwide,” said Rita Balice-Gordon, PhD, Muna’s chief executive officer, in Muna’s press release (2).

“By applying spatial multi-omics to unique patient phenotypes, Muna's MiND-MAP platform is able to determine the genetic and cellular basis of progression and resilience in neurodegenerative diseases. The alliance exemplifies our discovery ethos, to utilize advanced data and platform tech to identify high-confidence, human-data-derived, causal targets, which we can support with GSK’s scale and expertise in clinical development and commercialization, to bring desperately needed new therapeutic solutions in Alzheimer’s disease,” said Khavandi, in the Muna press release.

1. Relation. Relation Announces Two Strategic Collaborations with GSK to Advance Therapeutics for Fibrotic Diseases and Osteoarthritis. Press Release. Dec. 10, 2024.
2. Muna Therapeutics. Muna Therapeutics Announces Strategic Alliance with GSK to Accelerate Development of Novel Treatments for Alzheimer’s Disease. Press Release. Dec. 5, 2024.

With these agreements, the respective parties will work to advance therapeutic candidates for treating fibrotic diseases, osteoarthritis, and Alzheimer’s disease.

GSK Enters into Strategic Collaborations with Relation and Muna to Advance Drug Development

BioMarin Pharmaceutical announced on Dec. 9, 2024 that it plans to invest €60 million (US$63 million) into its Shanbally, Co. Cork., Ireland site to expand its state-of-the-art manufacturing facility. The company will use the investment to add a new, four-story laboratory, which will be used to increase production capacity for currently approved drugs and will allow for future growth, according to a press release (1).

The expansion adds to BioMarin’s footprint in Ireland. In addition to the manufacturing site in Shanbally, the company also operates a commercial office in Dublin and employs more than 500 people in Ireland. The company initially acquired the Shanbally manufacturing facility, which was at the time a bulk biologics manufacturing plant, from Pfizer in 2011 for US$48.5 million (2).

“This investment in our Cork facility reflects our ongoing commitment to enhancing our industry-leading global manufacturing capabilities and supporting the growth of our innovative medicines for our people living with rare conditions around the world,” said Evelyn Marchany Garcia, senior vice-president, chief quality officer, BioMarin Pharmaceutical, in the press release (1). “The Shanbally facility plays a crucial role in our global network, and this expansion emphasizes our confidence in Ireland’s skilled workforce and the strategic importance of this site to BioMarin’s long-term success."

The Shanbally facility represents BioMarin’s only manufacturing site outside of the United States. The facility’s capabilities include end-to-end manufacturing, producing therapeutics from bulk drug substance to drug product to final packaging. This €60 million (US$63 million) investment marks the second major significant expansion of the site. In 2023, BioMarin opened an aseptic production facility in Shanbally, which was a four-year build that enabled increased production of commercial and clinical products. The company invested €38 million (US$40 million) over four years to build the aseptic production facility (3).

“As a global leader in the biopharmaceutical sector, BioMarin’s ongoing investment in Ireland is a welcome endorsement of the country’s position globally as a location of choice for biopharmaceuticals and a trailblazer in advancing healthcare solutions. By opening this new quality control and process development laboratory, BioMarin will create new opportunities for collaboration, talent development and growth, ensuring that the life sciences sector in Ireland continues to make an impact on patients’ lives worldwide,” said Michael Lohan, CEO, IDA Ireland, in the press release.

“Expanding our laboratories allows us to deliver our medicines more efficiently and at greater scale for people living with genetic conditions. This latest investment reinforces our commitment to advancing treatment options and supporting patients across the world,” added Conor Delaney, site lead and vice-president of Shanbally Manufacturing Operations, BioMarin Pharmaceutical, in the release.

BioMarin has eight marketed therapeutics (4), including its first gene therapy, valoctocogene roxaparvovec, which was approved in Europe by the European Commission in August 2022 (5) and in the US by FDA in June 2023 (6).

1. IDA Ireland. BioMarin Announces Significant Investment and Expansion of Cork Facility. Press Release. Dec. 9, 2024.
2. BioMarin Pharmaceutical. BioMarin Agrees to Acquire Biologics Manufacturing Plant in Ireland from Pfizer. Press Release. June 23, 2011.
3. IDA Ireland. BioMarin Opens €38m Expansion of its Cork Manufacturing Site. Press Release. April 24, 2023.
4. BioMarin Pharmaceutical. Products. biomarin.com/products-and-pipeline/products/ (accessed Dec. 11, 2024).
5. BioMarin Pharmaceutical. First Gene Therapy for Adults with Severe Hemophilia A, BioMarin's ROCTAVIAN™ (valoctocogene roxaparvovec), Approved by European Commission (EC). Press Release. Aug. 24, 2022.
6. FDA. 

With this investment, BioMarin will add a new laboratory to its Shanbally, Co. Cork, Ireland, manufacturing facility.

BioMarin to Increase Production Capacity with €60 Million Expansion at Ireland Facility

Novo Holdings has received approval from the European Commission (EC) for its acquisition of Catalent and the subsequent related sale of three Catalent manufacturing sites to Novo Nordisk, Novo Nordisk announced on Dec. 6, 2024 (1). Novo Holdings is a holding and investment company responsible for managing the assets and the wealth of the Novo Nordisk Foundation. In earlier related news, Novavax announced on Dec. 4, 2024, that it signed a definitive agreement to sell its manufacturing facility in Bohumil, Czech Republic, to Novo Nordisk for $200 million (2).

Novo Nordisk had announced on Feb. 5, 2024 that it will acquire the three Catalent manufacturing sites from Novo Holdings upon completion of the Catalent transaction (3). These three sites are located in Anagni, Italy; Brussels, Belgium; and Bloomington, Ind., United States. The sites specialize in the sterile filling of drugs and employ more than 3000 personnel, all with ongoing collaborations with Novo Nordisk. Under the transaction, Novo Nordisk pays $11 billion upfront.

The acquisition of the three sites will be completed immediately following the merger of Catalent and a Novo Holdings subsidiary, which is expected towards the end of 2024. Until the close of the Catalent acquisition, Catalent will continue to operate independently and separately from Novo Holdings and Novo Nordisk. Following the close, Novo Nordisk will honor all customer obligations at the three Catalent sites it is acquiring (2).

Meanwhile Novo Holdings’ acquisition of Catalent is expected to be completed near the end of 2024, pending customary closing conditions, including regulatory approvals in other jurisdictions (1).

“We are very pleased with the agreement to acquire the three Catalent manufacturing sites which will enable us to serve significantly more people living with diabetes and obesity in the future,” said Lars Fruergaard Jørgensen, president and chief executive officer at Novo Nordisk, in a company press release issued at the time of the sites acquisition announcement (3). “The acquisition complements the significant investments we are already doing in active pharmaceutical ingredients facilities, and the sites will provide strategic flexibility to our existing supply network.”

The acquisition of these three Catalent sties will enable an expansion of Novo Nordisk’s manufacturing capacity at scale and speed and provides future options and flexibility for the company’s existing supply network. Novo Nordisk expects to gradually increase its filling capacity from 2026 and onwards through the acquisition of these sites.

Under the Novavax transaction, Novo Nordisk will gain that company’s Bohumil manufacturing site, which includes a transfer of assets such as a 150,000-square-foot state-of-the-art recombinant protein manufacturing facility, support buildings, and the existing workforce as well as all related and required infrastructure, for $200 million (2). This transaction is expected to close by Dec. 30, 2024, at which time Novo Nordisk will take over full responsibility for the manufacturing facility.

"The decision to sell the Czech Republic manufacturing facility aligns with our previously announced commitment to evolve Novavax into a more lean and agile organization focused on partnering our pipeline assets and technology platform," said John C. Jacobs, president and chief executive officer, Novavax, in that company’s press release (2). "We are thankful to our dedicated colleagues in the Czech Republic who have contributed to Novavax's mission of delivering our technology to address unmet needs. We look forward to working with Novo Nordisk to ensure a successful transition."

1. Novo Nordisk. The European Commission Approves the Acquisition of Catalent by Novo Holdings and the Related Acquisition by Novo Nordisk of Three Manufacturing Sites from Novo Holdings. Press Release. Dec. 6, 2024.
2. Novavax. Novavax Announces Sale of Czech Republic Manufacturing Site to Novo Nordisk for $200 Million. Press Release. Dec. 4, 2024.
3. Novo Nordisk. Novo Nordisk to Acquire Three Fill-Finish Sites from Novo Holdings A/S in Connection with the Catalent, Inc. Transaction. Press Release. Feb. 5, 2024.

The European Commission has approved Novo Holdings' acquisition of Catalent, which includes the related sale of three manufacturing sites to Novo Nordisk, which is also acquiring the Czech Republic manufacturing site of Novavax for $200 million.

Novo Nordisk Gains Manufacturing Sites from Novo Holdings and Novavax while EC Approves Catalent Acquisition

Novartis has entered into a global license and collaboration agreement with PTC Therapeutics (PTC) under which Novartis gets access to PTC’s PTC518 Huntington's disease program, which includes related molecules, the two companies announced on Dec. 2, 2024 (1,2). PTC518 is a huntingtin (HTT) messenger RNA (mRNA) splice modulator. It has the potential to become the first oral disease-modifying therapy for Huntington's disease, according to the Novartis press release (1).

Under the agreement, Novartis will pay an upfront payment of $1 billion and up to $1.9 billion in development, regulatory, and sales milestones. Both companies will share in profits and losses in the United States on a 40/60 basis (40% PTC and 60% Novartis) (2). Novartis will also pay PTC tiered royalties on sales outside the US (1). The transaction is subject to customary closing conditions, including regulatory clearance, and is expected to close in the first quarter of 2025 (2).

Novartis will assume responsibility for the development, manufacturing, and commercialization of PTC518 following completion of the placebo-controlled portion of an ongoing Phase II study (PIVOT-HD), which is expected in the first half of 2025. The agreement bolsters Novartis’ neuroscience pipeline and as the company focuses its efforts on neurodegenerative diseases with high unmet needs.

"PTC518 is the leading oral disease-modifying therapy in development for Huntington's disease and the economics of this agreement are consistent with the promise of this treatment," said Matthew B. Klein, MD, chief executive officer, PTC Therapeutics, in that company’s press release (2). "This collaboration combines PTC's expertise in developing small-molecule splicing therapies with Novartis's expertise in global development and commercialization of neuroscience therapies. We are excited to collaborate with Novartis to accelerate the potential of PTC518 for the hundreds of thousands of HD patients worldwide in need of a therapy designed to be well-tolerated and an effective disease-modifying therapy. PTC will use the proceeds of this transaction to expand our splicing platform as well as to support commercial and development portfolio activities."

PTC discovered PTC518 through its validated splicing platform. Interim results reported in June 2024 (3) from the ongoing Phase II study demonstrated that treatment with PTC518 resulted in durable, dose-dependent reduction in blood and cerebrospinal fluid mutant HTT levels. The interim results also showed early signals of a dose-dependent benefit on key clinical measurements at 12 months. More importantly, according to PTC, PTC518 has continued to demonstrate a favorable safety and tolerability profile (3).

"Huntington's [d]isease is a devastating, fatal, familial disease. This agreement with PTC is intended to bolster our neuroscience pipeline and reflects our strategic focus and commitment to explore new and potentially transformative approaches for neurodegenerative diseases with high unmet needs," said Vas Narasimhan, CEO of Novartis, in PTC’s company press release (2). "We look forward to building on our expertise in neurodegenerative diseases and experience in [Huntington's disease] with the intention to advance this potential first-in-class oral therapy for the [Huntington's disease] community."

1. Novartis. Novartis Bolsters Neuroscience Pipeline with In-Licensing of PTC518 for Huntington’s Disease. Press Release. Dec. 2, 2024.
2. PTC Therapeutics. PTC Therapeutics Enters into a Global License and Collaboration Agreement with Novartis for PTC518 Huntington's Disease Program. Press Release. Dec. 2, 2024.
3. PTC Therapeutics. Interim PIVOT-HD Results Demonstrate Evidence of Favorable CNS Biomarker and Clinical Effects at Month 12 in Huntington's Disease Patients. Press Release. June 20, 2024.

Novartis will in-license PTC's PTC518 program, which has the potential become the first oral disease-modifying therapy for Huntington's disease.

Novartis Enters $2.9 Billion License Agreement with PTC Therapeutics for Huntington’s Disease Development Program

Lipid nanoparticles (LNPs) have been gaining traction as a primary formulation and drug delivery tool in the manufacture of messenger RNA (mRNA)-based therapeutics, having proven their utility in the development of mRNA COVID-19 vaccines. As the development of LNP-enveloped mRNA therapeutics advances, what other nanoparticle technologies offer the opportunity for optimizing the formulation of mRNA—and potentially other nucleotide-based—therapeutics? This article explores the advancement of LNP formulations as well as additional nanoparticle technologies in this space.

Developing an mRNA therapeutic involves both the manufacture of the mRNA molecule itself and combining that molecule into some sort of delivery technology, whether that delivery technology is a LNP or other platform, says Colin McKinlay, PhD, senior director, Chemistry and Delivery Technologies, at Nutcracker Therapeutics. One of the challenges McKinlay points out is the type of approach a developer must take in manufacturing these types of drugs, which are unique in that they are personalized therapies, where every patient, each therapy, and the drug components are basically different.

“I think one of the lessons learned from the whole COVID-19 pandemic and putting together the mRNA-based vaccines for COVID-19 was that we could actually scale these [vaccines] up to worldwide scales, and that we were able to do that fairly effectively,” said McKinlay. “But starting to think about distributing and manufacturing mRNA drugs, where every patient has a different type of formulation, I think that starts to be a different type of challenge.”

Somewhat related to the logistics of distribution, McKinlay goes on to explain that many of the challenges associated with mRNA drug manufacturing are tied into having the ability to bridge smaller-scale companies—that is, their research work—into Phase I, Phase II, clinical-trial scale, and get these companies the materials they need for conducting those trials. “There are [many] commercial suppliers that are available for research-grade mRNA and for making mRNA at that small scale when [companies] are doing [their] discovery work. And obviously, if [a company] wants to invest a large amount of money into manufacturing, there are [many] opportunities available for large-scale commercialization, but getting strategies that are suited for … small clinical-trial stage where it is not too cost prohibitive upfront is something [where] there is a definite need in the market for,” McKinlay says.

With personal background experience in academia and moving up to a small startup and eventually to a mid-size startup, McKinlay relates the lessons learned in dealing with LNP manufacturing. “One of the things I’ve found throughout my career is that when you’re doing those initial discovery experiments and early stage experiments, you really want to be able to run high-throughput type experiments—screening different formulation chemistries, different combinations of components, or even different mRNA cargo types. However, at that small [of a] scale, [many] commercial options for making LNPs are not really tailored towards that small scale,” he explains.

In the course of his work, McKinlay noted that, although there are production systems available from various different suppliers, these systems generally have a rather large minimum volume or minimum scale at which they can operate. “What [many] people end up doing is to just pipette-mix or hand-mix their components, which means that the LNPs you’re making are very different than the LNPs you’re going to be making farther down in your development process during scale up,” he says.

One of the ways that a company can address this problem is by having its own engineering team in-house, McKinlay emphasizes. With this in-house capability, the company can have the team think about the challenges and ways to design LNPs on both a manufacturing level and at a system level. The results of the engineering team’s work can be used in research that is applied to much of the same core technologies. This gives the company the advantage of having information that can be translatable at every stage of development. “I think there are other companies that are starting to pick up on that importance,” McKinlay says, “but if you don’t think about that early on, you might end up optimizing for something that doesn’t end up being quite as good later on [and further] into your manufacturing process.”

Looking beyond the manufacturing challenges, innovations are in development to address these hurdles. McKinlay notes that some of those innovations are just starting to kick off. “The first wave [of innovation] has [involved the use of] a lot of the existing manufacturing technologies in the biologic space for these mRNA molecules. Now, [the industry is] actually starting to get different companies that are thinking about: how do we actually pursue this workflow for an mRNA specific platform? Not just pushing ourselves across the finish line, but really trying to adapt things to the advantages of mRNA and the unique challenges associated with mRNA?” he states.

McKinlay has also observed that some of the larger mRNA companies are starting to consider the problems in the mRNA space much more deeply with an aim to innovate in this space in a more mRNA-centric way. “For instance, one of the things I brought up earlier is the personalized medicines aspect. One of the exciting things about mRNA is some of the personalized therapies and personalized vaccines [that have come out of this space],” he remarks.

With a growing number of personalized medicines coming onto the scene, the industry is now looking at unique manufacturing challenges associated with them. “I think those are areas where we’re going to continue to see different types of innovation in the field,” McKinlay adds.

Broadly speaking, McKinlay considers the fact that not everybody is going in the same direction with mRNA therapeutic development an exciting trend. “There are a lot of different places that mRNA can be applied. In some cases, moving past the early stages of this field, one of the things that people are going to have to do is start specializing in different areas and saying, ‘Okay, this company is going to take mRNA in this direction.’ ‘This company is going to take it in a different direction.’ I think [this attitude] is one of the great things about a broad field like mRNA,” McKinlay says.

Vaccine development is an area where mRNA has truly demonstrated its effectiveness. But McKinlay points out the importance of not pigeonholing that platform technology such that mRNA is only thought of as a vaccine technology. Moving beyond infectious disease vaccines, or even COVID-19 vaccines, is going to be crucial to the growth of the mRNA field, McKinlay believes.

In terms of the LNP side of this field, McKinlay emphasizes that a number of LNP technologies exist that will focus on expression in the liver and that are directed towards the liver. “One of the [notions] that a lot of folks in the field are really focusing on is, ‘how do we actually direct these lipid nanoparticles to other organs in the body so that we can address other types of disease areas?’,” he says. Many companies are on this train of thought as well as researchers in academia, McKinlay explains. However, there has not been large-scale clinical successes in this area yet, he notes. “I think that’s definitely a place where more development is going to be taking place, and there’s going to be a lot of kind of handoffs between academia and industry in finding some strategies to address that,” he states.

Exploring other delivery vehicles and opportunities

In terms of non-viral RNA delivery, LNPS have largely dominated this field in terms of clinical approvals and later-stage development, according to McKinlay. However, he cautions against the industry getting stuck in these local maxima, “where the field does a lot of optimization, and [players] are able to climb in efficacy, but then [they] reach a point where there’s not too much [left] that [they] can really optimize anymore.”

Nutcracker’s exploration of alternative delivery vehicles has resulted in the company’s peptoid-based platform. According to McKinlay, these peptoids can be used in a traditional LNP-type formulation. “We’re able to branch away from traditional LNP type particles and have particles that are a little bit more unique to the chemistry of these peptoid molecules. We think that [this technology] is pushing us over, a little bit away from where the rest of the field is working; there may be a little bit more room to grow and a little bit more room to improve,” he states. McKinlay also believes that, with more and more people in the field exploring different respective local maxima, the industry as a whole can net benefit together by improving the overall safety and efficacy of the mRNA delivery vehicles that it has available to it.

Meanwhile, in academia there is also focus on using LNPs for other types of genetic cargo, such as other types of RNA or even DNA. “Beyond nucleic acids, there is also significant opportunities for using LNPs in, maybe, combination therapies, where you may have an mRNA molecule, but you also have a lipophilic, small molecule that you can incorporate into the LNP. By combining those two together, you can [potentially] see increased efficacy,” McKinlay says. “Regardless of what the future holds for mRNA therapeutics, a tight handshake between therapeutics discovery and manufacturing will be necessary for its success.”

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Vol. 48, No. 12
December 2024
Pages: 20–21

When referring to this article, please cite it Mirasol, F. Exploring Opportunities for LNP Delivery in mRNA. 

LNPs have gained solid ground as a drug delivery system for mRNA due to their success in the vaccines arena.