Aligning mRNA Progress with Regulatory Streamlining

BioPharm Peer Exchange

Technologies to develop and manufacture biopharmaceuticals continue evolving

Streamlining Bioprocesses with Automation

Technological advances are aiding manufacturers to streamline aseptic processes.

Speeding Up Aseptic Processes

Quality Considerations for Using AI in Bio/Pharma

Ask the Expert:

Sterile filtration and use of sterile single-use materials provide the best solutions depending on vector size.

Advances in Sterilization Technologies for Overcoming Viral-Vector Manufacturing Challenges

Feliza Mirasol is the science editor for 

Synaffix, a Lonza company, announced on Oct. 30, 2024 that it has licensed its antibody-drug conjugate (ADC) technology to BigHat Biosciences (BigHat), a US-based biotech company which will combine the Synaffix technology with its machine learning (ML) antibody design platform. Through the collaboration, the companies aim to develop a new ADC pipeline program.

Under the agreement, BigHat will receive target-specific access to Synaffix’s late clinical-stage, site-specific ADC technology platform. This platform enables transformation of antibodies into proprietary, best-in-class ADC products. Lonza’s acquisition of Synaffix in June 2023 (1) means that BigHat also gains access to Lonza’s DNA-to-investigational new drug (IND) ADC offering. This DNA-to-IND offering enables drug developers to receive all necessary current good manufacturing practice (CGMP)/non-CGMP ADC batches leading up to the first clinical trial. The service is housed under a single quality system that encompasses all critical development and manufacturing activities, including antibody production, bioconjugation, and drug product filling.

“The ADC space continues to develop and evolve, and our collaboration with BigHat exemplifies the continued strength and appeal of our best-in-class ADC technology. We are excited to be at the forefront of next-generation ADC R&D by joining forces with BigHat and its AI [artificial intelligence]/ML-enabled antibody discovery and development platform. BigHat is the ideal partner for Synaffix to collaborate with. We look forward to supporting BigHat with every step in the ADC development and manufacturing process under the Lonza umbrella,” said Peter van de Sande, head of Synaffix, in a company press release.

Milliner, which is BigHat’s AI/ML-powered antibody design platform, works by integrating a synthetic biology-based high-speed wet lab with state-of-the-art ML technologies into a full-stack antibody discovery and engineering platform. This platform is used to engineer antibodies with more complex functions and better biophysical properties. Using this approach reduces the difficulty of designing antibodies and other therapeutic proteins when developers look to tackle conditions ranging from chronic illness to life-threatening disease. The platform also offers significant speed to reaching candidate discovery and validation.

“We are pleased to announce this collaboration with BigHat for its next-gen ADC molecule, which shows how drug developers can benefit from a fully integrated suite of services across our Biologics division. The Lonza network has continued to adapt to the evolving ADC landscape, including the recent addition of a highly potent vial fill capability at our Stein (CH) [Switzerland] facility. This dedicated ADC drug product capacity expansion completes our offer for comprehensive, end-to-end development and manufacturing services for ADCs, simplifying the path from DNA-to-IND and beyond for our customers,” Jean-Christophe Hyvert, president, Biologics, Lonza, said in the release.

Through this collaboration with Synaffix/Lonza, BigHat intends to advance its next-gen ADC program. BigHat’s ADC program is at the IND-enabling stage and is on track to be the company’s first clinical-stage program. According to the press release, BigHat’s next-gen ADC was optimized using the Milliner platform. It is designed for maximum payload delivery to tumor cells and with optimal drug-like-properties. Incorporating Synaffix's ADC technologies, such as GlycoConnect, HydraSpace, and toxSYN, BigHat expects to further improve the safety and efficacy of its next-gen ADC.

"BigHat is leveraging our AI-driven antibody design platform, Milliner, to develop advanced biologics that provide safer and more effective treatments for difficult-to-treat cancers. We are excited to combine Synaffix’s conjugation and linker-payload technologies with our custom-designed antibody to create a next-generation ADC for patients with high unmet medical need," said Mark DePristo, CEO, BigHat Biosciences, in the release.

1. Lonza. Lonza to Acquire Synaffix and Strengthen Antibody-Drug Conjugates Offering. Press Release. June 1, 2023.

Articles

Lonza’s Synnafix has licensed its ADC technology to BigHat Biosciences, which will combine it with its ML design platform to generate newly designed ADCs.

Lonza’s Synaffix and BigHat Biosciences Team Up on Machine Learning-Designed ADCs

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Tosoh Bioscience–Separation and Purification announced on Oct. 28, 2024 the grand opening of its expanded European headquarters in Griesheim, Germany. The expanded office space includes a state-of-the-art demonstration and training area that will enhance collaboration with customers, according to the company. Tosoh Bioscience–Separation and Purification is a supplier of liquid chromatography products in the Americas and Europe. The company is a subsidiary of Tosoh Corporation in Japan, the parent of the Tosoh Group.

"We are excited to unveil our expanded office in Griesheim, which will serve as a hub for innovation and collaboration," said Romain Dabre, director—Global Product Management, Tosoh Bioscience–Separation and Purification, in a press release (1). "This new facility will allow us to better serve our customers and explore new chromatography techniques and applications."

In addition to the new office space, the company’s applications lab has been expanded to include dedicated space for ultra-high performance liquid chromatography bioanalytics, polymer analysis, multi-column chromatography, and batch process chromatography. A dedicated wet room will also be available to provide training for customers on packaging large-scale chromatography columns. There is also an instrument service area, and mobile lab benches provide flexible expansion design for sustainability.

“The flexible customer training floor will enable us to better train our customers in cutting-edge chromatography techniques,” Patrick Endres, head of EMEA Product Management, commented in the press release (1). “This space provides an optimal learning environment for our customers."

Jonas Wege, head of EMEA Application Lab, added, "Having built a flexible application lab allows us to be adaptable to any changes and fresh developments in the biopharma and polymer markets in the future. This flexibility ensures that we can continue to meet the evolving needs of our customers."

1. Tosoh Bioscience–Separation & Purification. Tosoh Bioscience–Separation & Purification Expands European Headquarters in Griesheim, Germany. Press Release. Oct. 28, 2024.

The expanded offices in Griesheim, Germany, feature a demonstration and training area.

Tosoh Bioscience Opens Expanded Headquarters in Germany

The Novo Nordisk Foundation announced on Oct. 23, 2024 that Gefion, a new artificial intelligence (AI) supercomputer built on an AI data center infrastructure known as NVIDIA DGX SuperPOD (1), is now operational in Copenhagen, Denmark. The system was launched at an event in Copenhagen and symbolically “turned on” by His Majesty King Frederik X of Denmark; Jensen Huang, founder and CEO of NVIDIA, a US-based supercomputing company; and Nadia Carlsten, CEO of the Danish Centre for AI Innovation (DCAI).

Following its launch, Gefion is being readied for customers, beginning with a pilot phase in which select customers interested in using AI will use it to accelerate innovation in many areas, from quantum computing to drug discovery to societal challenges, such as the transition to green energy.

“Gefion provides our Danish enterprises with entirely new opportunities,” said Morten Bødskov, the Minister for Industry, Business, and Financial Affairs, Denmark, in a press release. “Gefion will drive the advancement of the green transition, enable tailor-made solutions, and strengthen the competitive standing of our companies in the global market. In a time of heightened international competition, this supercomputer acts as a vital enabler for advancing Danish businesses into the future. This ground-breaking technology represents an important opportunity for Danish companies and researchers to develop innovative solutions to future challenges.”

A public–private partnership between the Novo Nordisk Foundation and the Export and Investment Fund of Denmark (EIFO) resulted in the establishment of the new supercomputer. This partnership funded and established DCAI, a new company that owns and will operate Gefion.

“It’s a remarkable achievement that it has taken only six months from announcement to completion of this complex state-of-the-art supercomputer,” said Carlsten. “I am extremely proud of the team that came together and collaborated to turn this vision into a reality, delivering a leading capability that is now ready for customers to start testing new use cases. Gefion is the game-changer that many innovators had been waiting for.”

Huang added in the release, “Denmark recognizes that to innovate in AI, the most impactful technology of our time, it must foster a domestic AI infrastructure and ecosystem. The Gefion supercomputer will supercharge the scientists of Denmark with local AI computing infrastructure to drive advancements in life sciences, climate research, and quantum computing.”

Gefion is powered by 1,528 graphic processing units (GPUs) (NVIDIA H100 Tensor Core GPUs) and is interconnected using networking (NVIDIA Quantum-2 InfiniBand). According to the press release, “Denmark up to now had no GPU-accelerated supercomputers, and a thorough consulting process with relevant stakeholders across the country had identified access to computing power as a key roadblock to progress in Denmark’s otherwise thriving AI-based research ecosystem.”

Digital Realty, a global data center provider, hosts the supercomputer in an AI-ready data center facility in Denmark, which is designed and built sustainably, running on 100% renewable energy, according to the press release. Gefion was assembled and installed by Eviden, a European-based high-performance computing company.

In addition to the Novo Nordisk Foundation’s funding, EIFO contributed DKK 100 million (US$15 million) and owns a 15% minority stake in DCAI.

“Establishing Gefion is a milestone, and it fits very well with the Novo Nordisk Foundation’s vision of improving people’s health and the sustainability of society and the planet, as it creates new opportunities and can accelerate finding new solutions to pressing challenges,” said Mads Krogsgaard Thomsen, CEO of the Novo Nordisk Foundation, in the release. “In the future, we must cooperate even more with exceptional partners from all over the world if we are to solve the enormous challenges facing not only our own countries but the planet.”

Researchers will have the opportunity to engage with expert teams from NVIDIA in selected flagship project areas to co-develop solutions to complex problems. These areas include pharmaceuticals and biotechnology research, accelerating the green transition; and developing fault-tolerant (i.e., error-free) quantum computing using an open-source hybrid quantum computing platform (NVIDIA CUDA-Q).

The Novo Nordisk Foundation has committed DKK 600 million (US$87.4 million) towards the initial costs of the center housing the new supercomputer, which has the potential to accelerate drug discovery innovation.

Novo Nordisk Foundation Announces Start Up of Denmark’s First AI Supercomputer Geared to Accelerate Drug Discovery Innovation

On Oct. 28, 2024, ViaNautis Bio (ViaNautis), a UK-based biotechnology company specializing in delivering targeted genetic nanomedicines, announced that it has entered into a collaboration with Eli Lilly and Company (Lilly) under which the companies will leverage ViaNautis’ proprietary polyNaut platform to develop precision therapeutics carrying genetic cargos. The aim of the collaboration is to precisely deliver these therapeutics to prioritized tissues so as to address significant unmet medical needs.

Under the agreement, Lilly will pay ViaNautis an initial upfront payment with the short-term potential of making additional payments, including research-based milestones. ViaNautis is eligible to receive further milestones and royalties contingent upon specific cargo-loaded polyNaut-based products entering clinical development and reaching and reaching commercialization.

“This collaboration with Lilly is a testament to our polyNaut platform, which is also driving a highly differentiated emerging pipeline for severe life-limiting diseases. Combining our scientific know-how to precisely deliver genetic nanomedicines targeting difficult-to-reach sites, with Lilly’s extensive drug development and commercialization expertise will accelerate the creation of novel therapies to improve patient outcomes,” said Francesca Crawford, PhD, co-founder of ViaNautis, in a company press release.

The company’s proprietary polyNaut nanovesicles are designed to precisely target specific tissues and cell types to deliver genetic materials. The technology aims to improve the current delivery of genetic medicines and hold the potential to transform treatment for various diseases, according to the company in the press release.

“I am very excited about our collaboration with Lilly to develop novel genetic medicines for patients in need. I want to thank [Crawford] and the team for their hard work in getting to this key milestone, and I look forward to working with Lilly to accelerate our shared vision of delivering targeted genetic medicines,” said Adi Hoess, MD, PhD, chief executive officer of ViaNautis, in the release. The company is currently working on a pipeline of therapeutics in the central nervous system and cystic fibrosis disease fields (1).

Nanovesicles are being researched as alternatives to extracellular vesicles (EVs) for various applications, including drug delivery. As mediators of intercellular communication, EVs have gained growing interest from researchers for their potential use in the field of regenerative medicines or as a drug delivery vehicle. However, because EVs are derived from stem cells or progenitor cells, their use is limited primarily due to a lack of efficient and scalable production methods (2).

As a result, researchers are turning to nanovesicles, particularly biofabricated cell-derived nanovesicles, as an alternative to EVs that are offer scalable, efficient, and cost-effective production (2). Meanwhile, further research has been underway to develop and test simplified and rapid production methods for cell-derived nanovesicles that offer advantages over traditional methods in terms of yield and cost-effectiveness (3), which are anticipated to offer new approaches to therapeutic drug delivery.

 (accessed Oct. 30, 2024).
2. Ilahibaks, N. F.; Lei, Z.; Mol, E. A.; et al. Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine. 

 (12),1509. DOI: 10.3390/cells8121509
3. Goh, W. J.; Zou, S.; Ong, W. Y.; et al. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems: a Cost-Effective Alternative. 

The collaboration aims to develop precision genetic medicines using ViaNautis’ proprietary polyNaut technology platform.

Lilly Forms Strategic Collaboration with ViaNautis Bio to Develop Novel Genetic Cargo-based Therapeutics

Chris Spivey is the editorial director of 

Marianna Tcherpakov, PhD, director of Business Development, CMC Services, at Frontage Laboratories, spoke on the CDMO’s role in tackling complex technical challenges to enable startup biotechs solve scale up problems.

A Look at CDMO–Biotech Partnerships and Tackling Complex Technical Challenges (BIO 2024)

Frontage Laboratories founder Song Li, PhD, currently the executive chairman, board of directors, at the company, first set up a testing laboratory in Thorofare, NJ, with a focus on analytical and bioanalytical testing that quickly established a reputation for expertise. That foundation of expertise seems to have stayed fairly well intact, and science—and scientists—driving projects forward appear to be the key selling point for this contract development and manufacturing organization (CDMO), which says of itself, “our scientific knowledge base, technical expertise and reputation for high quality services have been integral to our ability in turning our services into your solutions” (1). In speaking with the company’s staff at BIO 2024, Pharmaceutical Technology Group’s Chris Spivey discerned that the practical upshot for the company has been that Frontage Laboratories often attracts the more vexing or technically challenging projects, and as a result, the company’s teams are now well situated to deal with the more difficult of perplexing projects for which others may not be as well prepared. As an example of the company’s preparedness, it states on the resources section of its website that it uses a next-generation sequencing (NGS)-based method, called the Frontage PGx NGS Test, to rapidly determine the genotype of 300+ genes involved in absorption, distribution, metabolism, and excretion (2).

Talking with Spivey at BIO, Marianna Tcherpakov, PhD, director of Business Development, CMC Services, Frontage Laboratories, at BIO, outlined the general approach the company takes when working with clients. She emphasized that the company’s approach is always customizable and personalized to not only the science the client requires but also to their specific strengths and weaknesses as an organization. “We look at your project as our own product. We therefore offer fast delivery, fast responses to client questions, almost as if we are holding hands … Many come from smaller startups that need a lot of guidance. [This] can be technical, it might be regulatory, but it all relies on our very strong scientific base,” Tcherpakov said. “We are passionate about technology,” she added.

Many of the PhD staff at Frontage Laboratories have come from other companies in the industry, and Tcherpakov pointed out that these past experiences and learnings are often brough to bear on the current project challenge. “We understand how stressful it can be for the smaller biotech, and even middle-sized [biotechs], when you have a lot of deadlines. You have clinical trials submissions coming up, and you need to be on top of everything, and fast,” she said.

Touting their scientific backbone Frontage Laboratories advertises itself as “more than a CRO”, in that it is also a “full global pharmaceutical development organization. Frontage Laboratories offers a comprehensive suite of drug discovery and development services including chemistry, DMPK [drug metabolism and pharmacokinetics], preclinical safety/toxicology, and clinical trial services with strategic and regulatory support to effectively bring new lead candidates through the IND [investigational new drug] stage to Phase II” (3).

BIO 2024 was held on June 3–6 in San Diego, Calif.

1. Frontage Laboratories. Services & Solutions. 

 (accessed August 21, 2024).
2. Frontage Laboratories. Resource Library. 

 (accessed August 21, 2024).
3. Frontage Laboratories. About Frontage. 

Marianna Tcherpakov, PhD, is the director of Business Development, CMC Services, at Frontage Laboratories. Image courtesy of Frontage Laboratories.

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Frontage Laboratories' Marianna Tcherpakov, PhD, director of Business Development, CMC Services, discussed the CDMO’s role in enabling startup biotechs solve complex technical challenges for scale up.

MilliporeSigma, the US and Canada Life Science business of Merck KGaA, Darmstadt, Germany, announced on Oct. 29, 2024 that it is investing $76 million to expand manufacturing capabilities for antibody-drug conjugates (ADCs) at its Bioconjugation Center of Excellence facility in St. Louis, Mo. The investment includes scaling utilities and enhancing process and analytical development labs. The company hopes the expansion will provide support for early stage and commercial bioconjugates and create shorter turnaround times.

Included in the expansion is the upgrading of 34,000 square feet of space that includes process and analytical development, quality control, R&D, manufacturing, and logistics departments. Also included will be new labs, a dedicated manufacturing buffer preparation facility, and a cold storage and a good manufacturing practice (GMP)-controlled room temperature (CRT) warehouse.

“We are shaping tomorrow’s cancer care, today. With this investment, we are not just enhancing our capabilities; we are investing in our clients’ success by accelerating innovation and development to ultimately deliver novel therapies to patients more quickly,” said Benjamin Hein, head of Life Science Services, Life Science business of Merck KGaA, Darmstadt, Germany, in a press release (1). “ADCs represent a transformative approach to oncology, enabling targeted therapies that minimize damage to healthy tissues. As the market for this novel modality grows and the medical community adopts them as first-line treatments, it may mean that fewer patients need invasive treatments like chemotherapy and radiation that cause significant side effects.”

This current expansion builds on expansion efforts the company has completed during the past few years. The company opened a $65 million, 70,000-square foot facility in Verona, Wis. in 2022 that doubled the production of highly potent APIs for cancer treatments. According to the company, ADCs are promising drug modalities for cancer treatments.

“The ability of ADCs to reach and target diseased cells without damaging nearby healthy tissues is also demonstrating significant potential beyond oncology, particularly with innovative bioconjugates like antibody-oligonucleotide conjugates and radioimmunoconjugates. These bioconjugates are being explored for a variety of applications, including autoimmune diseases, infectious diseases, and neurodegenerative disorders. This expanding scope highlights the transformative role of bioconjugates in advancing personalized medicine across diverse therapeutic areas,” the company stated in the press release.

In other ADC news, MilliporeSigma launched the Mobius ADC Reactor in September 2024, a scalable single-use mixer specifically designed for ADC manufacturing. The company also launched ChetoSensar technology that addresses challenges in ADC solubility. The ADCore portfolio of advanced payload intermediates enables more efficient synthetic pathways for common payloads used in ADC, reducing development and manufacturing time.

MilliporeSigma also offers expertise in both clinical and commercial manufacturing such as clinical services to support investigational new drugs, commercial service to support commercially approved ADCs with bioconjugation or linker/payloads, and integrated services for viral vectors, lipids, messenger RNA manufacturing, and more.

1. MilliporeSigma. MilliporeSigma Invests $76 Million to Expand ADC Manufacturing for Novel Cancer Therapies. Press Release. Oct. 29, 2024.

The company is investing $76 million to increase ADC manufacturing capacity at its St. Louis, Mo. facility.

MilliporeSigma to Expand ADC Manufacturing for Cancer Therapies

Editor of Pharmaceutical Technology Europe

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Allogeneic cell immunotherapies have the potential to be useful across a broad range of therapeutic areas; however, these ‘off-the-shelf’ therapies face certain limitations that prevent their wide use. In particular, allogeneic therapies can potentially lead to host immune systems rejecting the donor cells and, in some cases, the donor cells are rapidly eliminated before they can perform their required therapeutic role (1).

To enhance allogeneic cell immunotherapies, genetic engineering approaches are being employed to target gene modifications and knockout genes that may cause elimination of donor cells. Clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (CRISPR-Cas9) has been used to successfully perform targeted editing; however, it does so by creating double-strand breaks (DSBs) in DNA, which may lead to chromosomal loss or structural variation (1).

More recently, a novel technology, base editing, is being used that does not cause DSBs. “Both CRISPR-Cas and base editing systems can be used to target gene modifications with great specificity, but using CRISPR-Cas to do this relies on DSBs, which can be disruptive and deleterious to the genes you're to this all of your editing, especially when you're trying to multiplex targets,” explained Shannon Hinsdale, scientist II—Biology R&D at Revvity, a diagnostics and technology company that supports technology platforms for the advancement of cell therapies into the clinic (2). “However, with the base-editing approach, you can still harness the targeting power of CRISPR-Cas without relying on DSBs. And you can modify genes through a number of ways; two of which we commonly use are through introduction of premature stop codons and alteration of splice sites.”

Focusing on Revvity’s Pin-point base-editing platform for her presentation, Hinsdale revealed that it is “a three-component system that relies on an RNA guided enzyme, an extended RNA guide fused to an RNA aptamer, and then an effector enzyme, such as the cytosine deaminase, that recruits an effector protein.” Hinsdale provided data demonstrating the performance of the base-editing platform in primary T cells as well as in induced pluripotent stem cells (iPSCs), highlighting its viability in multiplexing when compared with CRISPR-Cas9. “In our experience, this [viability] equates to about two times the number of total cells at day three post electroporation,” she said. “Additionally, when we look at fold expansion, whether we're looking at three or four targets, with the Pin-point system, there's no effect versus with the [CRISPR]-Cas9, traditional, wild type Cas9, we see that there is a decrease in fold expansion as the number of targets increases.”

“[With the Pin-point platform,] we can achieve efficient editing in T cells, greater than 75% target based without enrichment, 50% of all four proteins knocked out on the surface. We show a good safety profile for edited cells, and we show that [base-editing] can be used for complex engineering in both T cells and iPSCs,” she concluded.

1. Porreca, I.; Blassberg, R.; Harbottle, J.; et al. An Aptamer-Mediated Base Editing Platform for Simultaneous Knockin and Multiple Gene Knockout for Allogeneic CAR-T Cells Generation. 

2. Hinsdale, S. Engineering Allogeneic Cell Immunotherapies in a Single Intervention with the Innovative Pin-point Base Editing Platform. Oral Abstract Presentation at ASGCT’s Advancing Gene + Cell Therapies for Cancer Conference, Philadelphia, PA, Oct. 16, 2024.

Hinsdale’s presentation is available ‘on demand’ through the 

Shannon Hinsdale from Revvity presented data at the Advancing Gene + Cell Therapies for Cancer conference demonstrating that base-editing systems are safe and effective for complex engineering in both T cells and iPSCs.  

Using Base-Editing to Enhance Genetic Editing Capabilities

On Oct. 28, 2024, Monte Rosa Therapeutics, a Boston, Mass.-headquartered clinical-stage biotechnology company specializing in novel molecular glue degrader (MGD)-based medicines, announced that it has entered into a global exclusive development and commercialization license agreement with Novartis in a deal worth potentially up to $2.1 billion. The aim of the agreement is to advance vav guanine nucleotide exchange factor 1 (VAV1) MGDs, including MRT-6160, a Phase I drug candidate being evaluated in an ongoing single ascending dose (SAD)/multiple ascending dose (MAD) healthy volunteer study for immune-mediated conditions.

Under the agreement, Novartis will pay Monte Rosa $150 million up front in exchange for exclusive worldwide rights to develop, manufacture, and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, starting with the initiation of Phase II clinical studies of MRT-6160. Monte Rosa is also eligible to receive tiered royalties on ex-US net sales.

Novartis will be responsible for all clinical development and commercialization of MRT-6160, starting at the Phase II clinical phase. Monte Rosa, meanwhile, will remain responsible for completing the ongoing Phase I clinical study for the drug candidate. In addition, Monte Rosa will co-fund any Phase III clinical development. The company will also share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the United States.

“We are thrilled to announce this agreement with Novartis, a key player in immune-mediated conditions, and we are excited about the transformative potential it provides for Monte Rosa and MRT-6160. We expect this will accelerate and broaden the scope of clinical development of MRT-6160 to advance this unique, orally bioavailable modality while retaining substantial value for Monte Rosa. We believe the transaction validates our unique and industry leading QuEEN discovery engine, and it further increases our conviction to rationally design and develop highly selective and safe MGDs for undruggable targets, including in the areas of immunology and inflammation, metabolism, and genetic diseases,” said Markus Warmuth, MD, chief executive officer, Monte Rosa Therapeutics, in a company press release. “The financial resources provided by this agreement are expected to extend our operational runway, enable us to advance our pipeline to potential value-creating milestones and anticipated proof-of-concept readouts, and further leverage our QuEEN discovery engine.”

MRT-6160 is a potent, highly selective, and orally bioavailable investigational degrader of VAV1, which is known as a key signaling protein found downstream of both T- and B-cell receptors. According to preclinical studies, MRT-6160 demonstrated deep degradation of VAV1, which resulted in a significant decrease in cytokines linked to immune-mediated conditions. It also showed no detectable effects on other proteins. The candidate has shown promising activity in preclinical models of multiple immune-mediated conditions (1,2).

"Novartis has had a long-standing interest in molecular glue degraders, which offer the potential to tackle challenging biological targets. We are excited about their application in immunology and the early progress we have seen by Monte Rosa in this space and with MRT-6160. We look forward to advancing MRT-6160 and learning more about its potential to provide a new therapeutic option for people living with a range of immune-mediated conditions,” said Fiona Marshall, president, Biomedical Research, Novartis, in the press release. “Novartis is committed to bringing forward new therapeutic options for these patients, and we are happy to be working with Monte Rosa to harness the potential of this approach to address unmet medical needs.”

1. Cartwright, A.; Desai, F.; Vora, S.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model. Poster presented at Digestive Disease Week 2024, Washington, DC, May 21, 2024.
2.Cartwright, A.; Vora, S.; Gyger, L.; et al. MRT-6160, a VAV1-Directed Molecular Glue Degrader, Inhibits Disease Progression in a T-cell Transfer Mediated Colitis Model Concomitant with Reduced Calprotectin Expression. Poster presented at EULAR 2024—Annual European Congress of Rheumatology, Vienna, Austria, June 14, 2024.

The companies expect to accelerate the clinical development of MRT-6160, a Phase I drug candidate, as well as explore further therapeutic opportunities across multiple indications.

Novartis Signs Global License Agreement with Monte Rosa Therapeutics Worth up to $2.1 Billion to Advance MGD-based Therapeutics

Science laboratory test tubes, laboratory equipment | Image Credit: © BillionPhotos.com - © BillionPhotos.com - stock.adobe.com

Modifi Biosciences, a company formed in 2021 as a spinout of technology developed at Yale University, announced on Oct. 23, 2024 that it is being acquired by Merck, known as MSD outside of the United States and Canada (1). Modifi Biosciences develops direct DNA modification enabled cancer treatments. The novel class of small molecules target a DNA repair protein called O6-methylguanine methyl transferase (MGMT). The company’s research was published in 

in 2022 (2) and has had pre-clinical data amassed through a number of tumor models, including patient-derived xenograft models of gliomas.

“In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumors,” said Ranjit S. Bindra, MD, PhD, Modifi Biosciences co-founder, Harvey and Kate Cushing, professor of Therapeutic Radiology at Yale School of Medicine, and scientific director of the Yale Brain Tumor Center at Smilow Cancer Hospital, in a press release. “We are honored to have Merck recognize the potential of our science, and as an oncology company, they are perfectly positioned to advance our innovations through clinical trials and commercialization.”

“DNA repair defects are a frequent hallmark of tumor cells and a major cause of resistance to cancer therapy,” said David Weinstock, MD, vice-president, discovery oncology, Merck Research Laboratories, in the release. “The talented Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.”

“We designed our small molecules to have the ability to uniquely overcome clinical resistance mechanisms that have been known for decades but until now have been non-actionable. Additionally, we created the molecules in a manner which allows them to be rapidly progressed from bench-to-bedside,” said Seth Herzon, PhD, Modifi Biosciences co-founder and the Milton Harris ’29 PhD Professor of Chemistry in Yale’s Faculty of Arts and Sciences and professor of Pharmacology and Therapeutic Radiology at the Yale School of Medicine, in the release.

The acquisition agreement has Merck, through a subsidiary, taking possession of all outstanding shares of the company for $30 million with potential milestone payments up to $1.3 billion.

In other news by Merck, the company entered into a license and collaboration agreement in October with Mestag Therapetuics, a Cambridge, UK-based biotech company to identify novel targets for inflammatory disease treatments, using Mestag’s reversing activated fibroblast technology platform. The proprietary platform models the pathogenic role of fibroblasts in human disease.

“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 (3). “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.”

Modifi Biosciences. Modifi Biosciences Acquired by Merck. Press Release. Oct. 23, 2024.

Lin, K.; Gueble, S.E.; Sundaram, R.K.; Huseman, E.D.; Bindra, R.S.; Herzon, S.B. Mechanism-based Design of Agents that Selectively Target Drug-resistant Glioma. 

Mestag Therapeutics. Mestag Therapeutics Announces License and Research Collaboration with MSD to Identify Novel Targets for Inflammatory Diseases. Press Release. Oct. 8, 2024.

Merck is acquiring the Yale-spinout, which develops direct DNA modification-enabled cancer treatments. 

Modifi Biosciences Acquired by Merck

Retrofitting Facilities for Cell and Gene Therapy Production

In his episode of Ask the Expert, Peter Walters, Fellow of Advanced Therapies at CRB Group, discusses the retrofitting of older and/or solid-dosage facilities into sustainable cell and gene therapy manufacturing facilities. According to Walters, cell and gene therapy facilities can be made very lean and sustainable, with some being 100% electric.“A lot of that has to do with the fact that there isn't a huge utility draw for that process,” says Walters. “A lot of those materials are going to be typically purchased and either made off site and brought in, or are made on site, but are low water usage, low utility usage.”

Walters says that, when retrofitting a facility, air handling, air locking, and personnel flows are factors to consider. “Cell therapy facilities tend to have at least a handful of spaces that want to be very high classified, and so you're [going to] need not only the air handling—ability to push a lot of air through those spaces in a very clean manner—but the air locking to get the material segregation movements [and] the personnel flows to get into those highly classified spaces. As we talk about gene therapy, sometimes viral vector spaces want to be BSL [biosafety level] spaces. They want to have certain levels of segregation. It's not uncommon to see vector facilities that have [a] two-corridor system; one dedicated to the supply of materials and one dedicated to outgoing waste and outgoing materials, and that helps drive segregation of flows and materials through your facility. It can be difficult to find a facility that's set up in such a way [as] to facilitate an easy retrofit.”

Click the video above to watch Walters answer the following question:

We wish to retrofit our solid-dosage facility into a sustainable facility for cell and gene therapy commercialization. What kind of cost should we expect?

Peter Walters is Fellow of Advanced Therapies at CRB Group.

Welcome to the Ask the Expert video series. This series is an extension of the PharmTech Group’s long-running print column in which industry experts answer common quality and regulatory questions from the industry. This new video series will expand on topic areas to include development and manufacturing concerns to help those working in the industry better understand bio/pharmaceutical requirements. Have a question you would like answered? Send it to 

, and it may appear in a future episode or print column.

In this episode of the Ask the Expert video series, Peter Walters, Fellow of Advanced Therapies at CRB Group, discusses how facilities used for solid dosage manufacturing may be retrofitted into sustainable cell and gene therapy production facilities.

Pitfalls in Aging Facilities

® spoke with Kenneth LaRiviere, head of Engineering at Andelyn Biosciences, about how manufacturing biopharmaceuticals in an aging facility might cause regulatory and production problems. He also discusses what companies can do to be sure they are meeting good manufacturing practice standards.

Companies must be sure the facility they are using to manufacture biopharmaceuticals is capable of meeting environmental requirements, such as particulates, graded space, and air changes, according to LaRiviere. “Differential pressure is another critical parameter for operations in bioprocessing facilities,” he continues. “You must be able to maintain your pressure cascades as necessary to ensure cleanability and a clean environment for your operations. Laminarity and unidirectional flow are critical if you are working in a Grade A space and other things like temperature and humidity [are also important].”

LaRiviere states that particulates can be an issue in older facilities, and filters are, therefore, required. “Rooms have HEPA filters in them. So, generally speaking, the HEPA filters, for the most part, don't fail very often, but as facilities age, the frames, the housings that the HEPA filters are in can develop cracks and leaks,” says LaRiviere. “So that is just something that happens with age, and something facilities would need to maintain. And older fans have difficulty moving the required amount of air.”

The ability to clean a facility is imperative, according to LaRiviere, and older facilities may not be built for easy cleanliness the way newer buildings are in their design. “Cleaning is critically important. If you can't clean your facility, you really can't operate.”

Click the above video to watch the full interview.

BioPharm International spoke with Kenneth LaRiviere, head of Engineering at Andelyn Biosciences, about the possible problems that can arise when operating an older facility for biopharmaceutical manufacturing. 

Leaders in pharmaceutical industry discuss the latest news making waves in the pharmaceutical industry. 

Behind the Headlines, Episode 5: GLP-1 Shortage, Nobel Prize, RNA Editing, and More

 is a bi-weekly panel discussion examining the latest trends, readouts, and other factors that drive pharmaceutical news and innovation. Each episode features consultants, venture capitalists, scientists, patient advocates, and journalists discussing the prior weeks’ top news while seeking to highlight the more enduring lessons that hide behind the headlines.

In episode 5, panelists Laks Pernenkil, Principal Life Sciences at Deloitte; Brian Feth, CEO at Xcell Biosciences; and Alex Philippidis, Senior Business Editor at Genetic Engineering & Biotechnology News, go behind the headlines to understand why FDA felt it was time to remove 

 list (1) and how Catalent’s sale of a small molecule manufacturing facility (and incidentally its own headquarters) to expanding European company Ardena might affect future drug availability (2).

The panel also discussed Nobel Prize awards being given in the 

 field (3) and what that might mean in terms of growth, given a series of false starts and hurdles including the shelving of a hepatitis C therapy due to fears that microRNA might not compete commercially with traditional therapeutic approaches (4). The Nobel Prize in physics awarded to recognize advancements in artificial intelligence (5) was likewise considered from the perspective of how AI will bolster drug discovery and drug formulation, as well as help optimize drug manufacturing. 

Lastly, panelists discussed the emerging potential for novel protein replacement therapies on the heels of Wave Life Sciences’ positive clinical data for RNA editing to combat AAT protein deficiency (6), and how temporary and reversible RNA-editing approaches may confer additional benefits that further support this novel approach in the marketplace.

FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. FDA Drug Safety and Availability. October 2, 2024. 

https://www.fda.gov/drugs/drug-safety-and-availability/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize

Catalent signs agreement to sell Somerset, NJ oral solids facility. Catalent. October 14, 2024. 

https://www.catalent.com/catalent-news/catalent-signs-agreement-to-sell-somerset-nj-oral-solids-facility/

The Nobel Prize in physiology or medicine, 2024. 

https://www.nobelprize.org/prizes/medicine/2024/press-release/

Sparmann A and Vogel J. RNA-based medicine: from molecular mechanisms to therapy. 

https://www.nobelprize.org/prizes/physics/2024/press-release/

Wave Life Sciences Announces First-Ever Therapeutic RNA Editing in Humans Achieved in RestorAATion-2 Trial of WVE-006 in Alpha-1 Antitrypsin Deficiency. Press release. Wave Life Sciences. October 16, 2024. 

https://ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-first-ever-therapeutic-rna-editing

Laks Pernenkil, Brian Feth, and Alex Philippidis go behind the headlines to discuss the impact of recent news, including FDA’s drug shortage list update, Nobel prize winners in microRNA and AI, and a big-potential research win for RNA editing. 

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