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At AAPS PharmSci 360, Karunakar Sukuru, global vice-president, Catalent Pharma Solutions, discussed lipid-based formulations and tackling bioavailability challenges for oral biologics.

AAPS PharmSci 360: LBFs and Tackling Oral Biologic Formulations

® spoke with Karunakar Sukuru, RPh, PhD, global vice president of Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions, about the advantages and new challenges with lipid-based formulations (LBFs). Sukuru also discussed the challenges of addressing bioavailability in the search for developing oral formulations for biologics.

“Lipid-based drug delivery systems are not new,” Sukuru said, noting, though, that although lipid-based drug delivery systems exist, there is, today, an increased need for them, particularly considering that of the almost 8500 or so molecules—small molecular entities—in development, 70% of them are poorly bioavailable. “Because [these small molecules] are either poorly soluble, or poorly soluble and poorly absorbed, [that] is where the lipid-based formulation comes into play … they have a very demonstrated and valuable utility,” he stated. LBFs enhance bioavailability, so that a molecule may not necessarily need to have aqueous solubility.

Meanwhile, delivering biologics or proteins through an oral route is very challenging because of their high molecular weight. “[There] [are] certain limitations; the body does not allow absorb[tion of] these high molecular weights … with most monoclonal antibodies or biologics, they are in the hundreds of 1000s of Daltons [in size],” Sukuru pointed out. “However, there are a lot of efforts going on, and novel formation and answers are showing good promise, where they open the tight junctions, facilitating the absorption of the molecules,” he added. Another challenge he emphasized is stabilizing the biologic molecule once it is delivered to the intestine, where it would otherwise be destroyed by an acidic environment.

Attendees can visit Catalent at Booth #1141 at AAPS PharmSci 360, which is taking place on Oct. 20–23, 2024 in Salt Lake City, Utah.

Karunakar (Karu) Sukuru, RPh, PhD, Global Vice President, Rx Product Development, Pharma and Consumer Health, Catalent Pharma Solutions

Karunakar Sukuru (Karu) RPh, PhD is the global vice president of Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions. With over 29 years of experience in the pharmaceutical industry, he has led the development and manufacturing of various drug delivery systems and technologies and has been responsible for product development and execution of projects globally. Sukuru had technical oversight of more than a dozen contract development and manufacturing organizations worldwide while working at Endo Pharma. In his current role at Catalent, he works with hundreds of pharmaceutical clients, including leading biopharma companies, globally. He has developed innovative controlled-release platform technologies in softgel form (three granted patents) and has over 27 pending patent applications in the field of modified shell and fill suitable for capsules for enteric and colonic delivery and lyophilization. After completing his PhD in Pharmaceutics from IIT-BHU, India, in 1995, Sukuru began his career at Natco Pharma in India, where he developed a variety of oral dosage forms for two years. He then joined Banner Pharmacaps in India, and later in Banner Pharmacaps USA, he worked on softgel and gel enrobed tablets. Sukuru joined Endo Pharma in 2006 and Catalent in 2016 as the vice president of Product Development. He is also a registered pharmacist.

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At AAPS PharmSci 360, Karunakar Sukuru, RPh, PhD, the global vice-president-Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions, discussed lipid-based formulations and tackling bioavailability challenges for oral biologics.

Karunakar Sukuru, RPh, PhD, the global vice-president-Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions, spoke on recent challenges and trends in softgel formulations. 

AAPS PharmSci 360: Challenges and Trends in Softgel Formulations

® spoke with Karunakar Sukuru, RPh, PhD, the global vice-president-Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions, during AAPS PharmSci 360 to discuss recent challenges and trends in softgel formulations.

“Recent challenges are mostly related to enhancing the solubility and making those solubilized molecules stabilized in the systems, particularly in softgels, and enhancing the bioavailability,” Sukuru said. He noted that there is an increasing demand for non-animal products by the industry, particularly in Europe where gelatin, an animal byproduct, is used as a shell component. Although gelatin is a good material to use in terms of its ability to make robust, subgenerative capsules, it also has some disadvantages, such as cross-linking challenges, Sukuru pointed out. “That is where [there is need] to address both the non-animal byproduct need, using plant-based materials, as well as … the cross linking issues,” he stated.

, which is on Monday, Oct. 21, at 3:30 pm MT (2:30 pm PT, 5:30 pm ET), centers around the missed opportunity for superior bioavailability and the ability to develop moderated drug release products using softgels. “Softgel is one of the most versatile dosage forms, and you could deliver [a] drug through any orifice in the body, literally,” Sukuru said. “There are products that we manufacture commercially to deliver through oral route, ophthalmic route, nasal, otic, vaginal, and every route of delivery, but it's very underutilized. [Futhermore] there are a lot of myths and misconceptions about softgels being very expensive. No, they are not. In fact … compared to spray drying and some other bioavailability enhancing technologies, they are not.”

Attendees can visit Catalent at Booth #1141 at AAPS PharmSci 360, which is taking place on Oct. 20–23 in Salt Lake City, Utah.

Karunakar (Karu) Sukuru, RPh, PhD, Global Vice-President-Rx Product Development, Pharma and Consumer Health, Catalent Pharma Solutions

Karunakar Sukuru (Karu) RPh, PhD is the global vice-president of Rx Product Development, Pharma and Consumer Health, at Catalent Pharma Solutions. With over 29 years of experience in the pharmaceutical industry, he has led the development and manufacturing of various drug delivery systems and technologies and has been responsible for product development and execution of projects globally. Sukuru had technical oversight of more than a dozen contract development and manufacturing organizations worldwide while working at Endo Pharma. In his current role at Catalent, he works with hundreds of pharmaceutical clients, including leading biopharma companies, globally. He has developed innovative controlled release platform technologies in softgel form (three granted patents) and has over 27 pending patent applications in the field of modified shell and fill suitable for capsules for enteric and colonic delivery and lyophilization. After completing his PhD in Pharmaceutics from IIT-BHU, India, in 1995, Sukuru began his career at Natco Pharma in India, where he developed a variety of oral dosage forms for two years. He then joined Banner Pharmacaps in India, and later in Banner Pharmacaps USA, he worked on softgel and gel enrobed tablets. Sukuru joined Endo Pharma in 2006 and Catalent in 2016 as the vice-president of Product Development. He is also a registered pharmacist.

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.

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.