Pharma Matters Q&A

Revolutionizing Drug Delivery: Insights into Lipid Nanoparticles

A conversation with Jarlath Keating, CEO of Phosphorex, on the future of LNPs in pharmaceutical innovation.

By: Tim Wright

Editor, Contract Pharma

In recent years, lipid nanoparticles (LNPs) have emerged as a groundbreaking technology in the pharmaceutical world, revolutionizing the delivery of complex therapeutic molecules like RNA and DNA. Their ability to encapsulate and protect sensitive payloads has proven pivotal in overcoming long-standing challenges in drug delivery, from poor cellular uptake to enzymatic degradation. Notably, the success of mRNA-based COVID-19 vaccines has propelled LNPs into the global spotlight, underscoring their potential in advancing precision medicine and transforming healthcare.

In this exclusive Q&A, Jarlath Keating, CEO of Phosphorex, talks about the critical role of LNPs in drug formulation and development. From addressing their unique advantages and challenges to highlighting Phosphorex’s expertise and vision for the future, Keating sheds light on how his team is pioneering innovations in non-viral drug delivery systems.

Contract Pharma: Can you provide an overview of lipid nanoparticles (LNPs) and their role in pharmaceutical formulation and development? Why are they pivotal in drug delivery systems today?

Jarlath Keating: Lipid nanoparticles (LNPs) are advanced delivery systems designed to encapsulate and protect therapeutic molecules like RNA and DNA. Their key role is enabling the efficient transport of these payloads to specific cells or tissues, ensuring stability, bioavailability, and targeted delivery. They’ve become pivotal drug delivery systems, particularly with the rise of mRNA-based therapies, as they overcome traditional barriers like poor cellular uptake and enzymatic degradation.

CP: What are the most significant advantages of LNPs compared to other drug delivery technologies? What are the main challenges holding LNPs back?

Jarlath: LNPs offer unparalleled advantages, such as targeted delivery, the ability to encapsulate diverse payloads, and enhanced safety profiles compared to viral vectors. They also provide scalability and adaptability for diverse therapeutic modalities, including vaccines, gene therapy, and oncology treatments. However, challenges remain, including achieving precise targeting, maintaining stability during storage and transport, and addressing the complexities of scaling manufacturing processes while preserving quality and consistency.

Scientists performing a serial dilution to create a standard curve for the Ribogreen assay.
(Photo: Phosphorex)

CP: Could you explain Phosphorex’s expertise in LNP-based formulation and development? What sets Phosphorex apart in this space?

Jarlath: Phosphorex specializes in LNP-based drug formulation and development, with a deep understanding of nanoparticle engineering, encapsulation efficiency, and stability optimization. What sets us apart is our commitment to innovation and customization. We tailor solutions to meet the specific needs of each client, leveraging advanced techniques and analytical tools to ensure optimal performance and regulatory compliance.

CP: How does Phosphorex approach the challenges of scaling LNP formulation from preclinical development to clinical manufacturing?

Jarlath: The unique success indicators of each client’s program continuously guide our approach to scaling LNP formulations. Through robust scientific communication with the client, Phosphorex collaboratively maps a formulation and process development strategy tailored to each client’s priorities.

The core areas of focus for scale-up and cGMP engineering batch readiness include best-fit process mixing and multi-dimensional downstream purification optimization, as well as drug product stability. One of the initial challenges is selecting the appropriate mixing technology for LNP fabrication along with the specific operating parameters. To facilitate this process, Phosphorex has invested in the leading microfluidic and turbulent mixing options and has developed extensive know-how in scaling LNP formulations across these platforms. Another often overlooked, but significant challenge is the downstream processing of LNPs which includes the removal of ethanol, exchange of buffer salts/pH adjustment, concentration, and 0.2 µm filtration. Early in the development process, Phosphorex likes to establish feasibility of Tangential Flow Filtration (TFF), a scale-able unit operation for concentrating and diafiltering the intermediate LNP drug product, for each formulation as the process subjects the LNPs to additional shear which can have negative impacts on critical quality attributes including particle size and RNA/DNA encapsulation efficiency. 

Additionally, each process development and scale-up strategy for technology transfer to cGMP is bolstered by a carefully aligned risk mitigation plan. Desirable process durations and corresponding material stability is consistently evaluated throughout process optimization and qualification via advanced analytical techniques such as cargo integrity by capillary electrophoresis and lipid composition by HPLC-CAD.

Lipids/materials being thawed on the benchtop in the formulation laboratory. (Photo: Phosphorex)

CP: Phosphorex recently partnered with NOF Corporation. Can you elaborate on the nature of this collaboration and what it means for your customers?

Jarlath: Our partnership with NOF Corporation combines their industry-leading lipid expertise via their COATSOME SS ionizable lipid series with Phosphorex’s advanced formulation and development capabilities. This collaboration strengthens our ability to deliver cutting-edge solutions for LNP development, offering our customers access to best-in-class materials and an integrated approach to innovation.

CP: How is Phosphorex enhancing its cGMP capabilities to better support clients during the clinical development and manufacturing?

Jarlath: Phosphorex is actively investing in state-of-the-art cGMP facilities and infrastructure to support clients in early phase clinical manufacturing. This includes expanding our capabilities to include formulation production and fill finish services, stringent quality control measures, and compliance with evolving regulatory standards. Our mission is to deliver comprehensive expertise and capabilities in differentiated non-viral drug product design and manufacturing. We are committed to supporting the successful development and launch of novel non-viral therapies, all while providing an exceptional customer experience.

CP: LNP technology played a critical role in mRNA-based COVID-19 vaccines. How do you see the application of LNPs evolving in future therapies?

Jarlath: LNPs played a transformative role in enabling mRNA vaccines during the COVID-19 pandemic. Looking ahead, their applications are expanding into gene editing, oncology, rare diseases, and beyond. Phosphorex sees tremendous potential in advancing LNP technology to deliver therapies that were previously unattainable, pushing the boundaries of precision medicine.

Phosphorex’s analytical team discussing capillary electrophoresis method development ideas that utilize the BioPhase 8800. (Photo: Phosphorex)

CP: What is Phosphorex’s vision for the future of drug formulation and delivery using LNPs? What role does innovation play in this vision?

Jarlath: Our vision is to lead the charge in transforming the CDMO experience in non-viral therapy development and manufacturing for unprecedented credibility and reliability. Due to the barriers our field currently faces such as a complex intellectual property landscape, unique knowhow, tangible experience, and regulatory uncertainty, external development and manufacturing resources are largely underutilized across the field. Nonetheless, strategically equipped CDMOs like Phosphorex possess immense value to offer investigational therapeutic sponsors by facilitating faster entry to the clinic with reduced financial risk.

Through established expertise dedicated to non-viral therapeutics, Phosphorex is innovating the CDMO experience by delivering proactive consultative unit operations selection and risk contingency planning coupled with world class project management and customer service. Furthermore, through our Partnership with NOF Corporation we seek to mutually expand the role of LNP therapies beyond hepatic targets by facilitating access to unique lipid libraries and providing solutions for actively targeted LNPs. With this mission, Phosphorex sees the field of non-viral therapies poised for improved pre-clinical and clinical program success rates and wider treatment opportunities than ever before.

CP: Can you share a specific example of a successful LNP-based project that Phosphorex has worked on?

Jarlath: An example of a customer-sponsored project that Phosphorex supported involved the improvement of the final LNP batch quality for a novel co-encapsulated gene editing system, in a clinically precedented lipid formulation. The resultant formulation outperformed the target product profile in all criteria; mean particle size, PDI, % encapsulation efficiency, and freeze/thaw stability. We were able to confirm the mRNA integrity of both cargoes for the client by capillary electrophoresis.  The success of this project led to additional programs to explore new formulations.

CP: What excites you most about the future of Phosphorex and its contributions to pharmaceutical innovation?

Jarlath: The future of Phosphorex is bright, fueled by the opportunity to shape the next generation of pharmaceutical innovations. I’m most excited about the potential to make transformative therapies accessible to patients worldwide and to continue pushing the boundaries of what’s possible in drug delivery. Our team’s passion and dedication to excellence will undoubtedly drive this mission forward.

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