Feliza Mirasol is the science editor for 

Feliza Mirasol

Belgium-based EXO Biologics and its contract development and manufacturing organization (CDMO) subsidiary, ExoXpert, both innovators in exosome-based therapeutics and drug delivery solutions, announced on Dec. 2, 2024,  that ExoXpert has received good manufacturing practice (GMP) certification for its Liège, Belgium, manufacturing facility. At the same time, EXO Biologics achieved the loading of GMP-grade exosomes with messenger RNA (mRNA) and DNA payloads. Both achievements mark significant milestones for the development of exosome-based therapeutics (1).

According to a company press release, ExoXpert is the first European CDMO specializing in exosomes that has received GMP certification (1). The certification was awarded by the Belgian Federal Agency for Medicines and Health Products. Both BioWin, the Health Cluster of Wallonia, Belgium, and the Public Service of Wallonia have been strong supporters of EXO Biologics’ and ExoXpert’s growth, according to the press release.

“We have now achieved two critical strategic milestones by the end of 2024, which extends our continued progress in developing scalable, GMP-compliant solutions for exosome as therapeutic and drug delivery system. This extends our market leading position in the development of exosome-based technologies, unlocking new possibilities for drug delivery, gene therapy, and immunotherapy,” said Hugues Wallemacq, CEO of EXO Biologics, in the press release.

The importance of the GMP certification lays in the official status it gives to ExoXpert’s ability to produce exosomes according to the highest industry standards. The GMP-certified facilities enable EXO Biologics to internalize production of EXOB-001, currently in Phase I clinical development and the first global European Medicines Agency-approved mesenchymal stem cell-based exosome therapeutic in clinical trials. The certification also enables ExoXpert to offer exosome-specialized GMP capabilities internationally, including to current clients in the United States and European Union markets as well as future partners. ExoXpert also has the ability to activate additional cleanroom on demand. The greatest demand for exosomes currently is their use as a safe and non-viral drug delivery system for cell and gene therapy applications, according to the company press release (1).

The second achievement, the successful loading of mRNA and DNA payloads into GMP-grade exosomes, represents a critical step toward developing safe, efficient, and scalable exosome-based therapies for genetic material delivery. While small molecules and short nucleic acids (e.g., small interfering RNA and microRNA) have already been validated in an end-to-end GMP-like setting (2), EXO Biologics’ achievement demonstrates significant progress in the loading of larger molecules (i.e., mRNA and DNA) into GMP-grade exosomes that can then be used for third-party non-viral drug delivery applications. The company’s preliminary trials data have shown a retention rate up to 80% of the loaded DNA cargo upon exosome loading (1).

“The GMP certification of ExoXpert’s Liège manufacturing facility and the successful loading by EXO Biologics of mRNA and DNA into exosomes are major steps in bringing safe and effective exosome-based therapies to patients worldwide. We are now working on optimizing the loading technology to further reduce the manufacturing cost and strengthen the attractiveness of exosome therapeutics and manufacturing compared to alternative classical technologies. This will revolutionize the treatment of complex diseases, including cancer, genetic disorders, and viral infections,” Wallemacq said in the release (1).

1. EXO Biologics. EXO Biologics & ExoXpert Achieve Two Critical Industry-First Milestones for the Exosome Field. Press Release. Dec. 2, 2024.
2. Bhome, R.; Del Vecchio, F.; Lee, G-H.; et al. Exosomal MicroRNAs (exomiRs): Small Molecules with a Big Role in Cancer. 

, 228–235. DOI: 10.1016/j.canlet.2018.02.002

Articles

EXO Biologics and ExoXpert, an EXO Biologics subsidiary, have received GMP certification of a European manufacturing facility for exosomes and have successfully loaded mRNA and DNA payloads into GMP-grade exosomes for drug delivery.

Exosomes Field Advances with Milestones Achieved by EXO Biologics and ExoXpert

Lonza has expanded its services to support smart capsule companies developing orally delivered biologics. Oral biologics have unique development and manufacturing requirements, Lonza stated in a Dec. 3, 2024 company press release (1).

Smart capsules are designed to enhance precision, efficacy, and control. They use electronic or mechanical elements to deliver drugs to the stomach or intestine, and their mode of action has the potential to revolutionize the market for oral biologics, Lonza stated in its release (1). There are promising applications for smart capsules in diabetes, obesity, and other therapeutic fields.

To meet the needs of companies developing smart capsule-based therapeutics, Lonza has expanded its offering with a bespoke development and manufacturing service that is focused on the specific needs of smart capsules companies. Through this offering, Lonza leverages its expertise in highly customized capsule solutions that can be tailored to specific requirements, such as size, design, and lock mechanisms. The service also offers a variety of functionalities, including targeted release using a bi-layer manufacturing technology, which can be adjusted to the needs of the respective API.

“The strong market interest in this bespoke offering for smart capsules, marked by the first customer already on board and additional discussions in progress, reinforces the value of our approach,” said Bart Pelgrims, vice-president, R&D, Capsules & Health Ingredients, Lonza, in the release (1). “By ensuring every detail of development, which goes beyond formulation, we are confident in our ability to support smart capsule innovators to help shape the future of healthcare.”

Oral delivery of APIs has traditionally been the route of administration preferred by most patients worldwide. Oral administration has led to improved patient compliance and adherence as well as drug accessibility. Delivering biologics through an oral administration route represents a growing market, and one that is expected to exhibit a 35% compound annual growth rate from 2023–2028, according to Lonza in the press release (1,2). “Since most new drug entities face bioavailability challenges, exploring innovative delivery solutions to mitigate these challenges is of great value to drug developers and their patients,” Lonza stated in the release (1).

Meanwhile, Lonza has also expanded its bioconjugation capabilities at its Visp, Switzerland, site with the addition of two new manufacturing suites (3). In November 2024, the company announced that the new suites will provide additional manufacturing capacity for launch and commercial supply to address growing market demand.

The two new multipurpose 1200-L manufacturing suites and manufacturing-related infrastructure will be added to the site’s existing bioconjugation facility and will double capacity for the launch and commercial supply of bioconjugates. The company expects that the new capacity will be operational starting in 2028 and will generate approximately 200 new jobs (3).

1. Lonza. Lonza Launches Tailored Offering for Smart Capsules Companies Developing Oral Delivery Solutions for Biologic Drugs. Press Release. Dec. 3, 2024.
2. Market Report Manav AI. 

. Lonza Market Intelligence, 2023.
3. Lonza. Lonza to Expand Bioconjugation in Visp (CH) with Two Additional Manufacturing Suites. Press Release. Nov. 12, 2024.

With its new offering, Lonza can tailor services to support smart capsule companies with its bi-layer capsule manufacturing technology.

Lonza to Provide Tailored Offering for the Development of Oral Biologics Using Smart Capsules

Abzena announced on Nov. 19, 2024 that it is adding good manufacturing practice (GMP) cell-based potency assay services to  its Cambridge, UK, and San Diego, Calif., development and manufacturing facilities. By now including these services, the company boosts its early and late phase analytical capabilities while enhancing its bioassay offerings. The additional services allows the company to offer more comprehensive, streamlined, and cost-effective ways to access critical data faster (1).

GMP cell-based potency assays play a critical role in the quantitative measurement of biological activity of a biopharmaceutical. These assays are also necessary for assessing the payload cytotoxicity of an antibody-drug conjugate (ADC) (2) for both GMP product release and stability testing. Adding this capability to its toolkit gives Abzena the ability to provide precise and reliable data on drug potency as well as developability and characterization data to elucidate mechanism of action (MOA) and immunogenicity, both essential for regulatory submissions.

“We recognize that high-quality data is the cornerstone of effective decision-making. When it comes to early phase biopharmaceutical programs, especially ADCs, developers must have a reliable CRO [contract research organization] partner with the deep knowledge and technical capabilities required, and who can deliver the necessary data needed to successfully reach their next target inflection point,” said Campbell Bunce, PhD, chief scientific officer and Cambridge site head at Abzena, in the press release. “Our established expertise and reputation have allowed us to extend our early phase capabilities to include GMP cell-based potency services at our global sites, addressing a critical need for our customers. This significant milestone further demonstrates our commitment to providing comprehensive, end-to-end support for our customer’s next-generation programs that drive successful outcomes from discovery to the clinic and onwards towards commercial.”

All services at the company’s Cambridge site are fully integrated with its development and manufacturing services in its US facilities located in San Diego, Calif., and Bristol, Pa.

“Biological drug development requires robust analytical support across all phases of development. At Abzena, we’ve placed significant importance on building a state-of-the-art analytical toolkit because we understand the value that it provides to our customers,” said Sean O’Brien, senior vice-president and San Diego site head at Abzena, in the release. “Our goal is to help our customers optimize their drug development strategies, secure funding, and navigate regulatory pathways more effectively. We will continue to invest in our expertise and expand our laboratories so that our broader analytical offering can best support them in their mission to get life-changing medicines to patients.”

1. Abzena. Abzena Expands Analytical Capabilities to Include GMP Cell-Based Potency Testing Across US & UK Sites. Press Release. Nov. 19, 2024.
2. Wang, Z.; Li, H.; Gou, L.; Li, W.; Wang, Y. Antibody–Drug Conjugates: Recent Advances in Payloads. 

 (10), 4025–4059. DOI: 10.1016/j.apsb.2023.06.015

The company has expanded its early and late phase analytical capabilities by including GMP cell-based potency assays at its sites in Cambridge, UK, and San Diego, Calif.

Abzena Expands Analytical Services with GMP Cell-Based Potency Testing in US and UK

Sanofi has invested €40 million (US$42 million) into its Lyon Gerland bioproduction site in France to boost antibody production. As part of the investment, €25 million (US$26 million) is going toward dedicated production and development of a Thymoglobulin (anti-thymocyte globulin [rabbit]) second-generation product, the company stated in a Nov. 15, 2024 press release. Thymoglobulin is Sanofi's polyclonal antibody for treating transplant patients (1).

Also under the investment, more than €15 million (US$15.7 million) will be put toward internalizing and localizing the preclinical and clinical production of monoclonal antibodies for treating type 1 diabetes in France.

“With this significant investment, we are strengthening our footprint and leadership in bioproduction from France to serve our ambitions in immunology. Our Lyon Gerland site already holds a central place in the Lyon ecosystem of life sciences, and this investment serves as a new step to allow us to accelerate its increased role in serving patients in France and around the world,” said Charles Wolf, general manager France, Sanofi, in a company press release (1).

The company’s polyclonal antibody is an immunosuppressant that is manufactured exclusively at the Lyon Gerland site. Sanofi produces 1.6 million vials of Thymoglobulin at the site to treat approximately 70,000 patients per year in 74 countries (1). In anticipation of the growing number of transplant patients worldwide, the company has developed a new manufacturing process that will increase production capacity for Thymoglobulin, ensure reliable supply, and further improve the product's environmental impact. Modernization work started in the summer of 2024, and the first industrial batches are slated to be produced in 2025 with the first commercial batches expected to be available in 2027.

“Production of this medicine will continue in the meantime and in parallel, according to the process currently in force, which guarantees its availability for patients,” Sanofi stated in its press release.

The bioproduction platform at the Lyon Gerland site is also flexible, allowing the company to internalize production of an immunomodulatory drug for treating unmet need in patients with preclinical type 1 diabetes. This drug, which the company has not named in its release, was previously produced outside the European Union and not by Sanofi. The development of the bioproduction area to produce this drug will begin in early 2025. The first batches are expected to be produced by the end of 2025 and commercial marketing is expected to start in 2027 (1).

Overall, Sanofi has committed more than €2.5 billion (US$2.6 billion) to major projects since the COVID-19 pandemic. In addition, the company has invested more than €1 billion (US$1.05 billion) in bioproduction. The company ensures that 60% of its global production is within the European Union, it stated in its press release.

1. Sanofi. Sanofi Strengthens Antibody Bioproduction in France with an Investment of More Than 40 Million Euros On Its Lyon Gerland Site. Press Release. Nov. 15, 2024.

Sanofi will use this investment to increase its antibody bioproduction at its site in Lyon Gerland, France. 

Sanofi Grows Antibody Production in France with €40 Million Investment

Circio Holding, a Norway-based biotechnology company specializing in next-generation circular RNA (circRNA) vector technology for gene therapy, announced on Nov. 19, 2024, that it has entered into a collaboration with Spain-based Certest Biotec, an independent biotechnology company focused on the development and manufacturing of 

 diagnostic products. The companies aim to develop Circio’s circVec technology into lipid nanoparticles (LNPs) to be used in formulations of therapeutics that will enable tissue-specific delivery of DNA vectors for addressing genetic disease (1).

Certest has successfully performed packaging and 

 validation of circVec–LNP formulations that are targeted for delivery to lung, liver, and spleen tissue with positive technical results. Under the collaboration, Circio will next move on to test these circVec–LNP formulations 

 over the next three to six months. The goal is to assess delivery efficiency, expression level, and durability. If the experiments are successful, they may lead to the development of multiple in-house and partnered circVec therapeutic candidates for treating genetic diseases, according to a company press release.

“Circio’s powerful circVec-DNA technology achieves more than six months durability in mouse models on a single intra-muscular injection, with up to 15-fold increase in payload expression levels vs. standard mRNA [messenger RNA]-based vector systems,” said Victor Levitsky, MD, PhD, chief scientific officer (CSO), Circio, in the press release. “Based on these promising findings 

, we are now looking for targeted delivery technology that can enable therapeutic application of circVec in specific tissues and diseases of high unmet medical need. We selected Certest as a preferred partner for circVec–LNP formulation due to the impressive tissue specificity demonstrated for their proprietary nanoparticles.”

According to the release, Certest’s proprietary ionizable lipids and optimized LNP formulations have shown notable delivery specificity to several tissues of interest for Circio (lung, liver, and spleen). In addition, technical formulation and 

 analysis of circVec–LNP formulations by Certest have been successful, allowing the companies to advance to 

“The library of ionizable lipids developed by our team is engineered for a wide range of nucleic acid payloads, exhibiting a great delivery capacity in preclinical studies and allows the production of thermostable LNPs,” said Juan Martínez Oliván, PhD, CSO of Certest Pharma, specialized unit in nucleic acids delivery systems at Certest Biotec, in the press release. “Our capability to passively target different tissues unlocks the possibility to treat organ-specific diseases. We are very enthusiastic about the joint formulation of Circio’s new approach to circular RNA vector technology with our versatile ionizable lipids, creating a unique LNP-strategy for gene therapy treatment.”

Circio’s proprietary circVec technology is based on a modular genetic cassette design, which allows for efficient biogenesis of multifunctional circRNA from DNA and viral vectors. This circRNA can be deployed in multiple disease settings, including cell and gene therapy and chronic diseases, according to the press release. CircRNAs are a class of single-stranded RNAs that are being engineered as novel treatments for disease treatment and prevention (2).

1. Circio Holding. Circio Announces circVec LNP-delivery Collaboration with Certest Progressing to 

 Testing. Press Release. Nov. 19, 2024.
2. Niu, D.; Wu, Y.; Lian, J. Circular RNA Vaccine in Disease Prevention and Treatment. 

The companies will collaborate to create and test circVec DNA–LNP formulations for use in potential therapeutic applications.

Circio and Certest to Collaborate on LNP Formulations

Contract research organization BioPharmaSpec, which specializes in discovery and preclinical characterization of biopharmaceuticals, has officially launched three new European facilities in Freiburg, Germany; Bergamo, Italy; and Vilnius, Lithuania. These new facilities will focus on discovery and R&D services, according to a Nov. 12, 2024 company press release (1).

The facilities will offer structural and physicochemical characterization services for a variety of biopharmaceutical products, including monoclonal antibodies, antibody-drug conjugates, cell and gene therapy products, bioactive peptides, oligonucleotides, and carbohydrates. The company will also offer host cell protein identification and the quantitation of other relevant product- and process-related impurities at these facilities.

"Complementing a long career in academia where I’ve been the professor of Biological Chemistry at Imperial College since 1980, it has been a privilege to help drive forward this exciting development and significant expansion of BioPharmaSpec. The Freiburg, Bergamo, and Vilnius sites join our existing UK [United Kingdom] and US-based facilities to create the BioPharmaSpec Group of companies, serving the global biopharmaceutical industry,” said Prof. Howard R. Morris FRS, founder of the BioPharmaSpec Group of companies, in the press release (1).

The launch of these new facilities marks a significant milestone in BioPharmaSpec’s growth since it was founded in 2014 by Morris—who brought with him 45 years of experience in mass spectrometry discoveries and who was the founder of the M-Scan Group of companies—and Andrew Reason, PhD—who brought with him 25 years of experience in commercialization of analytical methods and who previously held the role of group manager of the European M-Scan laboratories. BioPharmaSpec now serves biopharmaceutical companies worldwide with its structural and physicochemical characterization services, which facilitates progress of drug pipelines, according to the press release (1).

“With the opening of these new laboratories in January 2025 and recruitment of local expert scientists, we are strategically and uniquely placed to provide our expanding global client base with the highest levels of technical and customer service," said Lindsay McGowan, director of business development at BioPharmaSpec, in the press release (1).

In addition to modern office space and meeting rooms, the new laboratories at the three facilities will host state-of-the-art instrumentation, Including accurate mass quantitation systems from Waters and SCIEX. (e.g., Waters Select Series CYCLIC ion mobility separation (IMS) high-definition liquid chromatography tandem mass spectrometry (LC–MS/MS) with electron capture dissociation, SCIEX ZenoTOF 7600 LC–MS/MS with electron-activated dissociation, Waters Xevo TQ Absolute, and Waters Xevo G3 LC–MS/MS quadrupole time-of-flights). The use of these high-end instruments combined with support from expert scientific advice, will enable access to high-quality structural characterization services with fast turnaround times, the company stated in its press release (1).

The company has also published recruitment announcements for scientists and technicians for the Vilnius and Freiburg sites (2,3).

1. BioPharmaSpec. BioPharmaSpec Announces Three New Facilities in Freiburg, Bergamo and Vilnius. Press Release. Nov. 12, 2024.
2. BioPharmaSpec. BioPharmaSpec is Recruiting: Scientists and Technicians- BSc or PhD (Vilnius, Lithuania). Press Release. Nov. 11, 2024.
3. BioPharmaSpec. BioPharmaSpec is Recruiting: Scientist- Masters or PhD (Freiburg, Germany). Press Release. Nov. 11, 2024.

Located in German, Italy, and Lithuania, the new European facilities  will specialize in drug discovery and R&D services. 