Feliza Mirasol is the science editor for 

Feliza Mirasol

Mestag Therapeutics (Mestag), a Cambridge, UK-based biotech company focused on gaining new insights into fibroblast-immune interactions, announced on Oct. 8, 2024 that it has entered into a new license and collaboration agreement with Merck & Co., known as MSD outside of the United States and Canada, to identify novel targets for developing therapies against inflammatory diseases.

Under the agreement, Mestag will provide Merck options to obtain exclusive licenses to develop and commercialize therapeutics directed against a prespecified number of potential targets identified in the collaboration. In return, Mestag will receive an upfront payment and access fees and will be eligible to receive option fees and downstream payment. The deal is valued at potentially $1.9 billion.

Mestag will use its reversing activated fibroblast technology (RAFT) platform to identify novel drug targets. RAFT is a proprietary platform designed to model the pathogenic role of fibroblasts in human disease. Merck has the option to license one or more targets, up to a prespecified number. Merck is also responsible for the discovery, development, and commercialization of therapeutics resulting from the collaboration.

“Mestag was founded on … insights into fibroblast–immune biology, and as an early innovator in this area of research, we have built a robust pipeline of antibody programs and created a unique and productive target discovery platform,” said Susan Hill, PhD, chief executive officer of Mestag, in a company press release. “We are acutely aware of the significant unmet needs faced on a daily basis by patients suffering from inflammatory diseases. We are thrilled to collaborate with [Merck], together driving continued innovation for the benefit of patients.”

With insights learned from fibroblast–immune interactions (1,2), Mestag specializes in developing impactful treatments for patients with cancer and inflammatory diseases. The company is progressing a pipeline of complex first-in-class antibodies designed to direct and drive the immune system. The company’s drug development work is based on known and emerging fibroblast–immune biology knowledge to create a distinctly differentiated class of therapeutics, according to the press release.

“The role of activated fibroblasts in directing immune activity offers exciting new therapeutic potential.We look forward to collaborating with the team at Mestag to identify new potential therapeutic options for patients with fibrosis and inflammatory diseases,” said Marc Levesque, MD, PhD, vice-president of Immunology Discovery, MSD Research Laboratories, in the press release.

Mestag’s pipeline includes a bispecific antibody, MST-0300, which operates on a new understanding of tertiary lymphoid structures (TLS) in solid tumors and TLS’ role in driving improved patient outcomes. The pipeline also includes M402, a program for a candidate that targets a stromal checkpoint to dampen activation of specific immune cell subsets in inflammatory disease, as well as earlier programs in the discovery stage. In addition, the company is separately identifying novel targets for future therapies using its RAFT platform. In 2024, the company established a license and research collaboration with Merck to identify novel targets for inflammatory diseases.

1. Wong, Z. Y.; Nee, E.; Coles, M.; Buckley, C. D. Why Does Understanding the Biology of Fibroblasts in Immunity Really Matter? 

 (2), e3001954. DOI: 10.1371/journal.pbio.3001954
2. Davidson, S.; Coles, M.; Thomas, T.; et al. Fibroblasts as Immune Regulators in Infection, Inflammation and Cancer. 

, 704–717. DOI: 10.1038/s41577-021-00540-z

Articles

Merck will deploy Mestag’s proprietary RAFT platform to investigate the pathogenic role that fibroblasts play in inflammatory diseases.

Merck to Collaborate with Mestag Therapeutics in $1.9 Billion Deal to Identify Novel Targets for Inflammatory Diseases

On Oct. 9, 2024, Evonik announced that it has won the 2024 CPHI Excellence in Pharma Award in the “Sustainability” category for its plant-based squalene, PhytoSquene, an adjuvant that can be used for parenteral drug delivery applications. According to a company press release, the product is the first plant-based squalene on the market that complies with good manufacturing practices (GMP).

Vaccines such as the H1N1 influenza vaccine use squalene as an adjuvant. Adding it to vaccines stimulates the body’s immune response to the active ingredient. Pharmaceutical-grade squalene is currently sourced from shark liver oil, however, which runs the risk of depleting shark populations and negatively impacting marine biodiversity, Evonik stated in its press release. “In terms of quality, animal-derived squalene may be susceptible to batch-to-batch inconsistencies which can complicate regulatory processes. Some patients also cannot use animal-based products for cultural or religious reasons,” the company also stated in the release.

PhytoSquene belongs to Evonik’s Next Generation Solutions (NGS) portfolio, in which products are categorized by a distinct sustainability profile. Evonik’s Health Care business unit aims to transform more than 70% of its portfolio by revenue to NGS by 2030. This goal also includes commitments from the company’s life sciences division, Nutrition & Care, to reduce the need for animal-derived products while growing its biosolutions portfolio, according to the company.

“Sustainability drives us! This award confirms that we are pursuing the right goals: to offer our customers alternatives that enhance patient outcomes and protect our planet,” said Yann d'Hervé, head of the Health Care business line at Evonik, in the press release.

PhytoSquene is manufactured in Germany using a proprietary process. It comes from amaranth (

) oil. Amaranth is an herbaceous plant cultivated in many parts of the world, making it a renewable feedstock. The manufacturing process produces consistent quality and is compliant with 

 regulations. Evonik launched commercial-scale PhytoSquene in 2023.

In 2022, Evonik won a CPHI Pharma Award in the category “Packaging and Drug Delivery” for a polymer-based messenger RNA (mRNA) drug delivery system. The drug delivery system is also used for delivery of other nucleic acid-based therapeutics.

Evonik also announced that it is transforming its Health Care business to focus on strategic core growth areas. Under the restructuring, Evonik will evaluate strategic options, such as partnerships or divestment, to develop its keto and pharma amino acid production sites in Ham, France, and Wuming, China. The company also plans to discontinue its production of keto acids in Hanau, Germany by the end of 2025 (1).

Evonik’s Nutrition & Care, the Health Care business within the company’s life sciences division, is transforming into a system solutions provider and is growing in core areas of expertise, including complex and highly potent APIs, oral and injectable drug delivery, and precision biosolutions, such as lipids for mRNA and gene delivery, and cell culture ingredients. The company described system solutions as tailored offerings that integrate products, technologies, and services with sustainability benefits, according to an Oct. 11, 2024 company press release (1).

For the full list of the 2024 CPHI Excellence in Pharma Awards winners, read the 

1. Evonik. Evonik to Restructure Its Keto and Pharma Amino Acid Business. Press Release. Oct. 11, 2024.

Evonik won the CPHI Excellence in Pharma Award in the “Sustainability” category in recognition of its plant-based squalene, PhytoSquene, used in parenteral drug delivery applications.

Evonik Wins Award at CPHI Milan for Plant-based Parenteral Drug Delivery Adjuvant

Nicolas Camper, senior director—Bioconjugation Chemistry, Abzena, discussed new advancements in ADC technologies, including the role of complex chemistries.

CPHI Milan 2024: New Developments in ADC Technologies

spoke with Nicolas Camper, senior director—Bioconjugation Chemistry at Abzena during CPHI Milan. Camper discussed the advancements in conjugation and linker technologies in antibody-drug conjugate (ADC) development and manufacturing. 

Nicolas Camper, Senior Director—Bioconjugation Chemistry, Abzena. Image courtesy of Abzena.

“There have been a lot of new developments in terms of conjugation and linker technologies. There is a definitive move towards site-specific conjugation technologies and away from stochastic conjugation approaches that allows [us] to prepare better-defined antibiotic-[drug] conjugates,” Camper said.

Another new development that has been observed over the past few years is that linkers are becoming more sophisticated. “Quite often, when you conjugate cytotoxic drugs, they are quite hydrophobic, and that can impact the performance of your ADC. So, there has been a lot of effort put into developing more hydrophilic linkers,” he noted.

Finally, another noticeable advancement in this area has been the development of branch linkers. Branch linkers give some options to prepare ADCs and modulate the drug loading, Camper explained. “[T]hat is something relatively new and should have an impact on the performance of ADCs and ultimately result in better ADCs and more programs,” he stated.

In his role at Abzena, Camper has scientific oversight of the group’s R&D activities focusing on ADC design and developability for external clients. His responsibilities involve technical management of pre-clinical ADC development projects from discovery stage to lead candidate selection. The group has expertise in synthetic chemistry, assembling linker-payloads, conjugation of the linker-payload to various types of protein carriers (primarily antibodies), and analysis of these bioconjugates.

Attendees can visit Abzena at Booth 18H11. CPHI Milan is being held from Oct. 8–10, 2024 in Milan, Italy.

Videos

Camille Dumont, PhD, manager, customer applications, Lonza, discussed current industry trends that are having an impact on development work in oral solid dose formulations.

CPHI Milan 2024: Industry Trends Impacting Oral Solid Dose Formulation

At CPHI Milan, Camille Dumont, PhD, manager, customer applications for Innovaform Accelerator at the Capsules & Health Ingredients business of Lonza, spoke with 

about bio/pharmaceutical industry trends and their influence on oral solid dose formulations. 

Camille Dumont, Manager, Customer Applications, Lonza. Image courtesy of Lonza.

“One of the trends we see with our customers, with the rise of inflamed bowel disease occurrence, is the oral delivery of live biotherapeutic products, which are originally administered for very invasive techniques,” she said. “[N]ow, we see lots of people working to have [these products] administered as a solid oral dosage form. Another important trend is the oral delivery of biologics such as peptides, proteins, mAbs [monoclonal antibodies], or mRNA [messenger RNA]. Most of these drug modalities are currently injected.”

Dumont pointed out that the injection route of administration can reduce patient adherence and can have a significant cost on healthcare systems. She emphasized that these types of APIs are fragile, however, and so require innovative solutions to achieve significant oral bioavailability. “Most of the time, only a combination of various strategies will result in [achieving] significant bioavailability and efficacy of these drug modalities, such as [using] enabling formulation devices and so on.

We offer formulation and targeted release capsule innovation to support this kind of need,” she stated.

To increase the bioavailability of many of these new drugs and new chemical entities, Dumont observed that there is a need for enabling formulation strategies, including permeation enhancers. “Recently, we have seen that a lot of biotechs [are] work[ing] on smart devices that are able to deliver fragile drug modalities directly by injection into the wall of the gastrointestinal tract. We can see that most of these innovations … rely on target release of the formulation … Solutions for target deliveries such as functional capsules appear as really interesting solutions for the pharmaceutical industry,” Dumont said.

With Lonza for about three years, Dumont is a chemical engineer with a PhD in pharmaceutical sciences from the University of Lyon, France. She has 10 years of experience in the pharma industry in developing innovative solutions for bioavailability enhancement, with particular expertise in lipid-based formulation and oral bioavailability enhancement of small and large molecules.

Attendees can visit Lonza at Booth 6A2. CPHI Milan is being held from Oct. 8–10, 2024 in Milan, Italy.

Results from the 2024 CPHI Annual Report suggest that contract manufacturing organizations (CMOs) and hybrid companies—companies having both their own pipelines and contract services for using spare capacity—will hold over half of global biologics capacity within the next three years. The results predict a dramatic shift from current (2024) global totals.

In 2024, total global biologics capacity is allocated as follows: nearly 60% controlled in-house, 28% held by CMOs, and 15% held by hybrid companies, according to the annual report. The report predicts that CMO capacity, which is rising fast, will account for 40% of total global biologics capacity by 2028, 45% of which will be located in Asia. The results suggest that capacity for new clinical products entering development may not be easily accessible in the United States, despite capacity being available. Europe and Asia combined are expected to account for approximately three-quarters of all available CMO resources in 2028, according to the report.

“Our Bioproduction Zone at CPHI Milan mirrors these findings. We are seeing a rapid increase in the numbers of bio CDMOs [contract development and manufacturing organizations] at our event, and we expect this be one of the fastest areas of growth in the next few years,” said Tara Dougal, Brand & Content director—Pharma, Informa, in a press release. “Particularly notable [in the report] is the rising capacity in Asia and among newer CDMOs.Many attendees visit specifically to start building their networks with these new partners.”

Over the past two decades, overall biologics capacity rapidly expanded from nearly 600 kL in 2000 to just above 6700 kL today; capacity is projected to grow to nearly 9000 kL by 2028, according to analysis provided by Dawn Ecker, managing director of bioTRAK Database Services at BDO. Insight from this analysis shows that, for the first time, CMOs will hold four of the top five capacities in 2028. Ranked in order from largest-to-smallest capacity holder, these CMOs are: Lonza, Samsung Biologics, FujiFilm Diosynth Biotechnologies, and WuXiBiologics. These four CMOs are estimated to control 34% of capacity between them. By 2028, CMOs will account for nearly 60% of global biologics capacity within the top 10 capacity holders, according to the annual report.

“The era of CMO production dominance is clearly arriving and is much needed, with many smaller companies now developing new biologics—especially mAbs [monoclonal antibodies]. This is significant for CPHI, where we see many more biotechs and early stage companies now attending to find suitable capacity—particularly for small production runs where they are more likely to partner with one of the hundreds of smaller CDMO partners. Helping find these ‘perfect fits’ is vital, and CPHI Milan is integral as a platform for meeting many different vendors, customers, and bioprocessing firms in one convenient location,” Dougalsaid in the press release.

CPHI Milan, held Oct. 8–10, 2024 in Milan, Italy, will host a panel on “Global Trends in Bio-Manufacturing” in addition to a number of important bio sessions and seminars as well as insights on “Optimizing Biologics Production with Single-Use Technologies” and lowering production costs with “cell line development” and “continuous bioprocessing”, according to the press release.

The full CPHI Annual Report will be released at CPHI Milan and will be made available for download at 

According to the annual survey, four of the five biggest biologics capacity holders in 2028 will comprise CMOs, which are expected to have 45% of all CMO capacity in Asia.

CMOs and Hybrid Companies Predicted to Hold 54% of Biologics Capacity in 2028, According to CPHI Annual Survey

Andrew Lewis, PhD, Chief Scientific Officer, Quotient Sciences, discussed the CMC challenges with GLP-1 and oral peptides during CPHI Milan.

CPHI Milan 2024: Navigating CMC Challenges for GLP-1 and Oral Peptides

During CPHI Milan, Andrew Lewis, PhD, chief scientific officer at Quotient Sciences, sat with 

 to discuss the chemistry, manufacturing, and control (CMC) challenges encountered during the development of glucagon-like peptide 1 (GLP-1) and oral peptides.

Lewis noted that a poor correlation seems to exist between the performance of oral peptides in preclinical animal studies and humans. “So, the approach we've pioneered at Quotient is to really tightly integrate our drug product manufacturing and clinical testing … by tightly integrating them, not only does it mean that we can rapidly advance [oral peptide products] into the clinic, but it also enables us, through the use of adaptive CMC clinical strategies, to modify formulations in response to emerging clinical data,” he stated.

Lewis also said that GLP-1s present tolerability challenges, and that this is true of this class of drugs as a whole. Permeability challenges can be addressed by the use of permeation-enhancing technology combined with modified release formulations, which may also enhance control of the pharmacokinetic profile and, hopefully, manage adverse events. “I think it's probably worth pointing out as well that, for oral peptides, they are particularly [used] with permeation enhancers. They are specific. They're very different formulations [from] a standard tablet formulation. You typically will require quite large amounts of permeation enhancers, so they make up a significant percentage of the formulation,” he explained. “Many of these permeation enhancers are quite waxy, [while] some of them are [somewhat] semi-solids.” These characteristics make permeation enhancers generally poorly compressible. In addition, they exhibit poor flow, which can make tableting or granulation difficult.

“There [are] certainly specific formulation and manufacturing processability challenges with oral peptides,” Lewis said. “Peptides behave very differently to small molecular weight drugs.”

You can visit Quotient Sciences at Booth A90 in Hall 7. CPHI Milan is being held from Oct. 8–10, 2024 in Milan, Italy.