Feliza Mirasol is the science editor for 

Feliza Mirasol

Watson-Marlow Fluid Technology Solutions (WMFTS), a manufacturer of peristaltic pumps and associated fluid path technologies, has launched WMArchitect, a range of flexible, single-use solutions for biopharmaceutical fluid management. This platform is built on the company's predecessor product lines, such as puresu and asepticsu. The new offering aims to streamline biopharma processing, safeguard product, and reduce regulatory burden, according to an April 15, 2024 company press release.

WMFTS now offers customized designs from its component library as well as a selection of standard, ready-to-use single-use assemblies. The WMArchitect offering represents an end-to-end, single-use fluid path management solution consisting of:

Customized designs: single-use assembliescan be custom-designed to meet specific requirements with an open architecture model that allows for flexibility and compatibility with existing fluid-contact materials already used in a company’s bioprocess.

Single-use fluid transfer assemblies: these fluid-transfer assembliesare ready-to-use, are pre-designed, and offer lot traceable tubing and components for optimizing fluid transfer between equipment and process steps. The latter can be selected from a menu of validated components.

Fill/finish single-use assemblies: these fill/finish assemblies are designed tosafeguard therapeutic products during the filling process using a range of sterility-assured assembly configurations. Representative assemblies are routinely tested to determine bioburden and presence of particulates and endotoxin.

Validation testing: WMFTS specialists offer support to WMArchitectusers using bioprocessing expertise and customized validation packages. The aim is to help reduce a company’s regulatory burden.

“By listening to the evolving needs of our biopharmaceutical customers, we have created WMArchitect to provide an expert solution that supports them in mitigating their regulatory and supply chain risks,” said Nicole Hunter, head of Global WMArchitect, in a company press release. “WMFTS understands that, often, off-the-shelf products are merely a starting point. We customize our standard products to provide a complete and tested solution from a single supplier that is tailored to meet a company’s specific requirements.”

WMArchitect is suitable for high-purity biopharmaceutical process development, clinical trials, and small-to-large-scale production batches. The most critical component for maximizing performance is at the point where the tubing meets the pump, the company acknowledged in its press release. In recent years, single-use components such as tubing, connectors, and valves have allowed for more 

. For instance, single-use tubing, connectors, and valve components can eliminate cleaning-in-place (CIP) and sterilizing-in-place (SIP) procedures. Removing these steps, which are often costly, time-consuming, and contribute to downtime, can increase manufacturing throughput and productivity of a facility. Furthermore, the time and personnel once used for CIP/SIP (e.g., of stainless-steel process lines) can then be reallocated to other areas of production, thus increasing overall efficiency of the manufacturing process (1).

WMFTS’ assembly solutions are designed synergistically with the company’s peristaltic pump technologies and filling solutions to ensure reliable, repeatable performance for even sensitive processes. In addition, a dedicated WMArchitect business unit offers benefits such as reduction of validation burden, support of internal validation protocols, an open architecture approach that allows flexible integration, synergistic use with the company’s peristaltic pumps of filling systems, and supply security based on the company’s global manufacturing and supply network.

The company will be showcasing its WMArchitect single-use solutions line at INTERPHEX, held in New York City on April 16–18, 2024.

Fluid Handling Systems are Seeing Benefit from Single-Use Technologies

Articles

WMFTS has launched WMArchitect, a single-use product line that offers ready-to-use single-use assemblies and custom-designed workflows for biopharma fluid management. 

WMFTS Showcases New Single-Use Solutions Designed to Optimize Fluid Management 

Much of the current development of messenger RNA (mRNA) in the biopharma industry is focused on using mRNA-based therapeutics in the targeted treatment of cancers. Obstacles still persist, however, in the delivery method of the therapeutic. One solution lies in the formulation stage, where, for instance, lipid nanoparticle (LNP) technology has become a common mode of delivery, owing to its success in the mRNA-based COVID-19 vaccines. In an interview with Stefaan De Koker, vice-president, Technology and Innovation, etherna, 

® explores the criteria that make mRNA a good choice as a therapeutic and looks at how LNP technology is becoming a well-established vehicle for delivering mRNA. 

Evaluating the Partnership between mRNA and LNPs

Pharmaceutical Technology’s Innovations in mRNA eBook

According to De Koker, mRNA combines three significant advantages compared to other drug modalities. First, mRNA is an extremely flexible platform. For instance, mRNA sequences can be easily modulated, and, hence, they can encode virtually any therapeutic protein, “whether it’s in the cytosol of the cell, on the membrane, or even a secreted protein,” said De Koker. The ability to easily modulate mRNA sequences was on reason why mRNA was well suited to a pandemic case, such as COVID-19. It also makes mRNA well suited for developing personalized immunity, such as, a cancer vaccine. In this instance, the vaccine can be adapted to the antigen profile of a tumor.

A second major advantage of mRNA is the ease of manufacturing, says De Koker. It can be produced quickly, which, again, was exemplified by the COVID crisis, where, within a few months, mRNA vaccines were in clinical studies, he emphasizes. “They were also clearly much faster to reach approval compared to more conventional therapeutic modalities, [such as] protein-based vaccines or viral vector-based vaccines,” De Koker adds.

The reason behind mRNA’s quick synthesis is that production can be done entirely 

, and thus there is no need for cells to produce it, De Koker emphasizes. mRNA manufacture is based on an 

 transcription reaction, which uses a viral polymerase to amplify the mRNA. Moreover, De Koker explains, mRNA contains only four building blocks, which means it has constant physical and chemical properties. “Thus, regardless of the protein [one] wants to encode, [they] would have the same physical/chemical properties. This, [therefore], allows [one] to develop generic manufacturing processes,” De Koker says.

A third beneficial aspect of mRNA is the fact that the immunogenicity of the platform can be modulated. “This means that the mRNA and the formulation can either be made less (for therapeutics) or more immunogenic (for vaccines) based on the application. It really makes the immune system believe that the viral infection is ongoing, and it needs to respond to that infection by mounting a strong immune response,” De Koker explains.

“These three things together—the flexibility, the speed of manufacturing, and ability to modulate the immunogenicity of the platform—makes mRNA a versatile platform for vaccines and other uses,” De Koker states.

When referring to this article, please cite it as Mirasol, F. Evaluating the Partnership between mRNA and LNPs. 

Pharmaceutical Technology Innovations in mRNA 

The LNP success in mRNA vaccines leads to their establishment as a standard in mRNA delivery.

In back-to-back agreements, Charles River Laboratories International will provide plasmid DNA (pDNA) manufacturing services to Axovia Therapeutics and Ship of Theseus. Announced on April 9, 2024, the Axovia agreement involves the manufacture high quality (HQ) gene-of-interest plasmid, which will support Axovia’s development of gene therapies for ciliopathies, including Bardet-Biedl Syndrome (BBS). Under the Ship of Theseus agreement, announced on April 4, 2024, Charles River will offer its expertise to manufacture pDNA to serve as the active drug substance for that company's lead candidate. 

Axovia is working on a lead program, AXV101, an adeno-associated virus serotype 9 (AAV9)-based gene therapy. The therapy targets retinal dystrophy associated with BBS. In preclinical studies, the gene therapy was shown to modify the underlying disease and halt retinal degeneration, stopping BBS-induced weight gain and the development of obesity. FDA granted orphan drug and rare pediatric disease designations to Axovia for AXV101. In the deal, Axovia will utilize Charles River’s plasmid platform, eXpDNA, and pDNA manufacturing expertise.

“We are committed to supporting Axovia in the pursuit of creating treatment options for patients living with ciliopathies. The Charles River team brings decades of expertise in HQ plasmid development, and we look forward to using these capabilities to make a difference for patients,” said Kerstin Dolph, corporate senior vice-president, Global Manufacturing, Charles River, in a company press release.

Ciliopathies are caused by cilia dysfunction resulting from genetic mutations that cause defective or dysfunctional cilia in many organs. Dysfunctional cilia can lead to blindness, deafness, chronic respiratory infections, kidney disease, heart disease, infertility, obesity, and diabetes. According to the press release, more than 20 ciliopathies have been identified. Collectively, they affect an estimated 1 in 1000 people.

“This collaboration brings us closer to accomplishing our goal to develop potentially transformative therapies for ciliopathies. We are excited to leverage Charles River’s expertise in plasmid DNA production to help drive our work forward,” said Victor Hernandez, co-founder and chief scientific officer, Axovia, in the release.

Meanwhile, Ship of Theseus, a therapeutics company specializing in degradation-resistant homeobox (HOX) family biologics, is developing a proprietary suite of biologics based on HOX family transcription factors. These transcription factors are responsible for directing the differentiation of tissue stem cells towards their respective lineages for the repair and maintenance of correct tissue and organ function. According to a company press release, “proprietary modifications may enable these regulators to be used as therapeutics.”

Under the collaboration, Charles River and Ship of Theseus will develop therapeutics for a broad variety of target indications such as diabetic and chronic wounds, neutropenia, psoriasis, androgenetic alopecia, women’s health and infertility, and epithelial cancers. This collaboration will be led by Charles River’s good manufacturing practice (GMP) pDNA contract development and manufacturing organization center of excellence in Keele, United Kingdom. The Keele site will provide pDNA backbone generation, plasmid synthesis, GMP master cell bank generation, pre-production evaluation, and GMP pDNA manufacture, including in-house release testing.

“Ship of Theseus is proud to collaborate with Charles River as our manufacturing partner of choice. We trust the team’s decades of success developing, producing, and reliably delivering plasmid DNA and look forward to bringing our therapies to patients,” said Jeremy Elser, founding CEO, Ship of Theseus, in the press release.

Source: Charles River Laboratories International for 

Charles River has entered into separate agreements with Axovia Therapeutics and Ship of Theseus to offer plasmid DNA manufacturing services for a gene therapy and a lead candidate program, respectively.

Charles River to Provide pDNA Manufacturing Services in Two Deals

Memel Biotech, a Lithuania-based contract development and manufacturing organization, announced on April 4, 2024 that it has launched a fully integrated advanced therapy development and manufacturing service at its facility in Klaipeda, Lithuania, which will serve markets in the European Union (EU). With this new service, the company aims to target partnerships with emerging and established biotech companies seeking to enter the advanced therapy medicinal product (ATMP) space. The company will operate a new good manufacturing practice (GMP) facility, where it will offer discovery-to-delivery service for all three classes of ATMPs: cell therapy, gene therapy, and tissue-engineered therapy.

Memel has built its technical expertise in product formulation, process and analytical development, process scale-up and automation, GMP manufacturing, validation, and logistics. The company has also maintained up-to-date knowledge of regulatory approval demands and processes in key markets, according to a company press release. The company’s manufacturing range encompasses mesenchymal stem cells, induced pluripotent stem cells, extracellular vesicles, immune cells (including natural killer cells and dendritic cells), and gene modified cells, including chimeric antigen receptor T cells.

“Advanced therapies have enormous potential to make life changing impacts on patients, but there is no escaping the fact that they are complex and challenging to manufacture and deliver,” said Agnė Vaitkevičienė, CEO, Memel, in the press release. “Based on our previous experience in the sector, we believe Memel has the portfolio of services and skills to meet the challenges companies that are aiming to make a difference face—from initial formulation to scale-up—whilst conforming to the still emerging regulatory framework. In addition to European clients, our location also offers an ideal EU entry point to [the] US [United States] and ROW [rest of world] companies.”

 under a project to be launched by the Northway Group, a collection of 17 enterprises within the fields of medicine, healthcare, biotechnical formation, and investment operations. In November 2023, the group announced its plans to build BIO CITY, expected to be the largest biotechnology hub in Europe and home to six large biotechnological complexes. Four of the complexes will be state-of-the-art GMP plants, and two will be scientific research centers. With a total area equivalent to the size of 10 football fields, BIO CITY is expected to cost €7 billion (US$7.6 billion) over the next decade (1).

According to Olga Potapova, president of the Cureline Group, a US-based company that provides management of scientific and pre-clinical research, development of diagnostic products, and organization of biological and tissue testing, “Memel is a natural extension of the [Cureline] Group’s portfolio. We have closely followed the development of the advanced therapies sector over the last decade in particular. Rather than try to repurpose any existing CDMO we believe the time is right to create a truly specialized partner who can take an active role in helping customers achieve their missions to bring these exciting new treatments to patients. Lithuania, with its highly skilled workforce, supportive environment, stability, and EU membership, is also an ideal location.”

1. Northway Biotech. The Largest Biotech City in Europe Will Soon Be Built by Northway Healthcare Group, with an Investment Amounting to 7 Billion Euros. Press Release, Nov. 16, 2023.

With the launch of a new manufacturing service, Memel Biotech will offer services for discovery through to formulation for advance therapy medicinal products.

Memel Biotech to Offer ATMP Manufacturing at Lithuania Site

Lonza and Acumen Pharmaceuticals, a clinical-stage biopharmaceutical company specializing in therapeutics that target toxic soluble amyloid beta oligomers (AβOs) for treating Alzheimer’s disease (AD), have formed a collaboration for Lonza to manufacture sabirnetug (ACU193), a monoclonal antibody (mAb) that targets toxic soluble AβOs. Sabirnetug is in clinical development for treating AD and will soon be entering Phase II studies, the companies announced in an April 4, 2024 press release.

Under the agreement, Lonza will manufacture sabirnetug drug substance at its manufacturing facility in Portsmouth, NH. The Portsmouth facility is equipped with 2000-L single-use bioreactors.

“Our collaboration with Acumen showcases our flexibility in enabling innovative biotech companies to advance their innovative therapies on accelerated timelines. We are excited that our new, next-generation single-use manufacturing facility in Portsmouth (US) will be used to manufacture a [C]GMP [current good manufacturing practice] drug substance that could bring new treatment options to patients suffering from Alzheimer’s disease,” said Stefan Egli, global head of Mammalian Biologics, Lonza, in a company press release.

According to the press release, sabirnetug is the first humanized mAb to demonstrate selective target engagement of AβOs in a Phase I first-in-human study. AβOs are known to be an early trigger and persistent driver of AD-associated synaptic dysfunction and neurodegeneration. Sabirnetug operates by preventing toxic AβOs from binding to dendritic spines and by preserving neuronal function, thus addressing an underlying cause of AD, according to the release.

“As we progress into Phase [II] clinical development of sabirnetug as a potentially best-in-class treatment for early AD, we are acutely aware that patients and their families are in urgent need of safe, effective treatment options for this devastating disease. Partnering with Lonza is a critical step to ensure broader access to next-generation AD therapies,” said James Doherty, president and chief development officer, Acumen Pharmaceuticals, in the release.

Regulatory support for the development of AD therapeutics was further advanced this year with the issuance of FDA’s 

 on early AD treatment in March 2024 (1). The guidance document is intended to aid sponsors who are in the clinical phases of developing therapeutics for treating the early stages of AD before dementia becomes overt. The March 2024 draft guidance is a revision of the February 2018 guidance; the draft remains open for comments until June 10, 2024.

In the past, enrollment in clinical trials for AD treatments were based on clinical criteria that defined the later stages of AD, and because of this, study subjects “exhibited both the cognitive changes typical of clinically evident AD and the degree of functional impairment associated with overt dementia,” according to FDA’s guidance document. Approved treatments were thus based on that context. However, FDA expects the new draft document to create discussions between the Office of Neuroscience in the Center for Drug Evaluation and Research, the Office of Therapeutic Products in the Center for Biologics Evaluation and Research, sponsors, the scientific community, and the public, where appropriate (1,2).

Draft Guidance for Industry, Early Alzheimer’s Disease: Developing Drugs for Treatment

 (CBER, CDER, March 2024).
2. Haigney, S. 

FDA Gives Guidance on Developing Treatments for Early Alzheimer’s

Under a collaboration agreement, Lonza will manufacture sabirnetug, Acumen Pharmaceuticals' mAb in clinical development for treating Alzheimer’s disease.

Lonza Forms Agreement to Manufacture Acumen Pharmaceuticals’ AD mAb Therapy 

In a deal expected to close in the first half of 2024, Genmab will acquire clinical-stage biotechnology company ProfoundBio for $1.8 billion in an all-cash transaction, according to an April 3, 2024 press release. ProfoundBio specializes in developing next-generation antibody drug conjugates (ADCs) and ADC technologies for certain cancers, such as ovarian cancer and other folate receptor alpha (FRα)-expressing solid tumors.  

Under the deal, Genmab will gain worldwide rights to ProfoundBio’s portfolio of next-generation ADCs, which includes three clinical programs and multiple preclinical programs. Clinical programs include Rina-S, a FRα-targeted, topoisomerase 1 (Topo1) ADC currently in the Phase II stage of a Phase I/II clinical trial. Rina-S is being evaluated for treating ovarian cancer and other FRα-expressing solid tumors.

The acquisition will also combine ProfoundBio’s ADC technology platforms with Genmab’s proprietary antibody platforms, potentially creating new opportunities to generate and develop new oncology therapeutics. 

Jan van de Winkel, president and CEO, Genmab. Image courtesy of Genmab.

“The proposed acquisition of ProfoundBio firmly aligns with our long-term strategy and our ambitious 2030 vision to impact the lives of patients through innovative antibody medicines,” said Jan van de Winkel, president and CEO, Genmab, in a company press release. “We believe that ProfoundBio’s ADC candidates, proprietary technology platforms, and talented team will be a great addition to Genmab and that, together, we will be able to accelerate the development of innovative, differentiated antibody therapies for cancer patients.”

The addition of Rina-S to Genmab’s portfolio will additionally strengthen the company’s presence in gynecologic oncology and allow it to build a foundation in solid tumors. This would be possible because Rina-S aims to address a broader patient population than first-generation FRα-targeted ADCs. Based on data from the ongoing Phase I/II clinical trial, Genmab will aim to expand development plans for Rina-S within the ovarian cancer space as well as with other FRα-expressing solid tumors. Rina-S was granted fast track designation by FDA in January 2024 for treating patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

“Genmab shares our team’s mission of developing novel therapies to improve outcomes for cancer patients. Genmab’s deep expertise in antibody drug development and commercialization makes this a compelling union that will allow us to rapidly develop and realize the full potential of our ADC therapies to benefit patients,” said Baiteng Zhao, ProfoundBio’s co-founder, CEO, and chairman of the board, in the press release.

In recent months, major biopharma players have also made significant moves toward building up ADC capabilities. In December 2023, 

 formed an $8.4 billion collaboration with SystImmune to co-develop and co-commercialize lead ADC candidate for cancer treatment in United States (1). In March 2024, 

 completed its $2 billion acquisition of Ambrx Biopharma, a clinical-stage biopharmaceutical company, which gives J&J the opportunity to design, develop, and commercialize targeted ADCs with Ambrx’s proprietary ADC technology platform. The platform utilizes highly specific-targeting monoclonal antibodies with a potent chemotherapeutic payload (2).

1. Bristol Myers Squibb. SystImmune and Bristol Myers Squibb Announce a Global Strategic Collaboration Agreement for the Development and Commercialization of BL-B01D1. Press Release, Dec. 11, 2023.
2. Johnson & Johnson. Johnson & Johnson Completes Acquisition of Ambrx. Press Release, March 7, 2024.

Genmab's acquisition of ProfoundBio will boost its clinical and preclinical pipeline of ADCs for targeted cancer treatment.