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Feliza Mirasol

Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation, discussed trends in new analytical tools for RNA characterization and gave highlights of his talk at AAPS PharmSci 360.

AAPS PharmSci 306: Trends in New Analytical Tools for RNA Characterization 

® at AAPS PharmSci 360,Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation, discussed some major trends in the development of new analytical tools for RNA characterization. Addepalli pointed to DNA sequencing technologies, which have pushed the sequencing of RNA too.

“Those technologies are referred to as next-generation sequencing; the problem with the next-generation sequencing is that it's an indirect sequencing method,” Addepalli stated. “That means the RNA is converted into DNA, so … you would lose some information during this conversion process. We need to do direct sequencing of RNA, [and] that's what people have realized while analyzing these RNA drugs and RNA therapeutics.”

“There are a lot of ambiguities in the sequence interpretation and data accuracy, so that's where … new tools and software can come into the picture,” Addepalli also said. “Having … enzymes that would improve the sequence coverage, and … a simple sample preparation method can help reveal the full information. That's where the trends are being focused, on analytical characterization [and on] how to simplify the process of RNA characterization through direct methods. [Those are] the major trend[s] that's been going on currently.”

Addepalli also highlighted some key points in his presentation at AAPS PharmSci 360, which is on 

Oligo Mapping of Large RNA Therapeutics by Novel Enzyme Specificities

: “I'm going to talk about … enzymes, [their] properties and their applications in characteriz[ing] large RNA therapeutic drugs, [such as] single guide RNA that is used in genome editing, and mRNA [messenger RNA] as part of the LNPs [lipid nanoparticles] that are used for vaccinations, or cancer therapies, or protein replacements,” he said.

Attendees can visit Waters Corp. at Booth #2438 at AAPS PharmSci 360, which is being held on Oct. 20–23, 2024 in Salt Lake City, UT.

Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation

Bala Addepalli, Bala_Addepalli@waters.com, is currently working as director of the Evaluations and Application Science Team under New Modalities (Cell and Gene Therapy product analysis) portfolio of Waters Corporation. His interests include development of simpler but efficient approaches for cell and gene therapy products such as messenger RNA (mRNA), lipid nanoparticle (LNP), and adeno-associated virus (AAV) analysis through liquid chromatography coupled with light scattering and mass spectrometry-based detection techniques.Prior to joining Waters, Addepalli developed novel enzymes and analytical methods for characterization of cellular RNA and modified oligonucleotides through mass spectrometry at University of Cincinnati. Before that he worked on RNA processing events including mRNA polyadenylation at University of Kentucky, and viral RNA characterization through mRNA translation for his graduate studies at Indian Agricultural Research Institute, New Delhi, India. Bala has authoredover 60 publications in peer-reviewed scientific journals and has delivered oral presentations at scientific meetings.

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AAPS PharmSci 306: Trends in New Analytical Tools for RNA Characterization

Bala Addepalli, PhD, Director, R&D New Modalities Portfolio, Waters Corporation, discussed recent advancements and current challenges in the development of large RNA therapeutics.

AAPS PharmSci 360: Advancements and Challenges in Large RNA Therapeutics

® sat with Bala Addepalli, PhD, director, R&D New Modalities Portfolio, Waters Corporation, at AAPS PharmSci 360, which is taking place Oct. 20–23, 2024 in Salt Lake City, UT, to discuss the challenges seen in large RNA therapeutics as well as their challenges.

Addepalli pointed out that there is much interest by industry in developing RNA-based drugs for treating genetic disorders, especially after the success of messenger RNA (mRNA), which was used to develop COVID-19 vaccines. He also noted that pharmaceutical vendors and companies are developing mRNA vaccines for other viral diseases such as influenza or as a combination of COVID and influenza vaccines. Furthermore, mRNA vaccines are also part of protein replacement therapies for patients who have deficiency in enzymes or proteins.

Meanwhile, challenges in the large RNA therapeutic space include inadequate analytical tools, Addepalli said. “The analytical tools that are currently available are inadequate, in a sense; they would provide only incomplete or partial information, so the purity and identity of the molecule is not fully revealed. And it also necessitates development of complex procedures in order to get such information,” he stated. And, he further explained, when specialized procedures and complex techniques are employed, the cost of development and manufacturing goes up, “and that leads to accessibility issues,” Addepalli added.

Attendees can visit Waters Corp. at Booth #2438 at AAPS PharmSci 360.

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

*Editor's note: updated on March 3, 2025 to fix typographical error.

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 antibody-[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.

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.