How CDMOs keep pace with trends in advanced therapies –

Advanced treatments including cell and gene therapies are exploding in demand, but the manufacturing process can be difficult. Jean-Christophe Hyvert, president of biologics and cellular & gene at the CDMO Lonza, sheds light on the latest trends in advanced remedies and how manufacturers are usually keeping up.

In 2021, global funding going to cell and gene therapies smashed records , totaling $23. 1 billion. This has been accompanied by a surge popular for manufacturing of these advanced therapies and other emerging modalities such as antibodies and microbiome therapeutics.  

To meet this growing demand, major contract development plus manufacturing organizations (CDMOs) like Lonza Group and Fujifilm Diosynth are investing big cash to scale up their capacity. Earlier this particular year, for example , Lonza invested CHF 500 million ($517 million) in a new Swiss manufacturing facility and expanded its Chinese and U. S. facilities to grow its offerings in order to customers around the world.

The field associated with advanced therapies continues to evolve, and manufacturers must maintain pace along with the speed of progress. New technologies are emerging each decade, including different types of antibodies; personalized cell therapies derived from the patient’s own cells such as CAR-T ; and gene therapy delivery vectors with improved organ tropism — the particular ability to affect selected organs plus avoid other tissues.

Lonza’s president of biologics and cell & gene, Jean-Christophe Hyvert, spoke to us about the most interesting sophisticated therapies upon the horizon in addition to exactly how manufacturers are usually adapting their processes in order to incoming innovations. Hyvert joined Lonza within 2017 plus had originally qualified as a physicist and worked in operations, before moving into a financial role.

One trend that stands out is the increasing number associated with bispecific antibodies (bsAbs) entering the clinical pipeline. BsAbs can be described as molecules that recognize two different antigens or epitopes, compared to conventional monoclonal antibodies (mAbs) that can only identify one. BsAbs range through small proteins – two linked antigen-binding fragments – to large immunoglobulin substances with other attached domains.

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To date, a total of 273 bispecific molecules have successfully entered the clinic since 2001, and they can play a significant part for patients receiving cancer care outside traditional treatment environments. We expect bispecific proteins plus other complex protein formats to dominate the drug development pipeline in the next 5 to 10 years.  

This biotherapeutic class offers improvements in therapy precision and flexibility — factors that have played decisive roles in the pursuit associated with bispecific treatments by medication developers. Leveraging familiar modes of administration, bispecifics may play the meaningful function for individuals receiving malignancy care outdoors traditional treatment environments, potentially creating inroads to access with regard to patients unable to travel to receive care.

We also see rapid growth in the field of in vivo gene treatment, with several therapies nearing late-stage medical readouts. Scalable manufacturing platforms will be key in ensuring sufficient commercial supply regarding emerging methods. New vectors are being designed to improve organ tropism and reduce immunogenicity, plus Lonza has been involved in developing scalable manufacturing systems for these new technologies.  

Another important trend is the particular exponential increase of mRNA-based development projects. This pattern is driven by the scientific and industrial success of the 2 mRNA-based COVID-19 vaccines, validating this promising technology after years associated with development.

The main advantages associated with mRNA-based compounds over some other modalities include the low amount of drug needed for a biologic effect, the opportunity of creating one manufacturing platform for multiple different mRNA compounds and finally, the ability of mRNA – using the right carrier, such as lipid nanoparticles  – to enter into tissues which is usually not possible for protein-based therapeutics. The intracellular mode associated with action is expected in order to allow the therapy of diseases that so far could not be tackled, like genetic diseases where patients lack intracellular protein.

A recent trend is also using mRNA to code Cas9 enzymes or even gene-editing enzymes. Applying this mRNA together with guide RNA – both encapsulated in LNPs – opens a new and possibly better tolerable avenue intended for ex vivo and in vivo gene therapy, as shown in a first clinical trial in sufferers with transthyretin amyloidosis.

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Another growing trend is the rise of exosome-based remedies . Exosomes are membrane-bound nanovesicles produced by almost every cell type to regulate metabolism and interact with other tissue within the body. These new therapies leverage the particular ability associated with exosomes in order to interact along with specific tissues to deliver drugs or naturally occurring regenerative and anti-inflammatory molecules to diseased cells. Being produced by cellular material, exosomes do not trigger adverse immune reactions and their own targeted delivery limits drug toxicity plus improves efficacy. Exosomes can be engineered to load multiple therapeutic modalities, including viruses, to get multi-drug restorative strategies or to engage with the immune system pertaining to immune treatments or vaccine development.  

Up to now, there are more than 50 exosome therapies within the pipeline. More than 80% are at the preclinical stage, and no products are commercially available yet. In the next decade, we expect exosomes to become a dominant non-viral vector modality, especially in therapeutic indications where targeted delivery and repeat dosing are required to achieve sustained effectiveness.  

How is the growing use of personalized cellular therapies changing the way the manufacturing process works?

Personalized cell-based therapy is considered one of the most effective treatments meant for patients diagnosed with cancer or hereditary diseases. Its effectiveness is due to therapies being created along with specific patients in mind – making it both a very effective treatment and a complex one to develop.  

Unlike other therapy options plus modalities, for example antibody-based remedies, personalized medicines are difficult for patients to access – they are generally only available at specialty hospitals, require complex supply chains and may require 3- in order to 4-week vein-to-vein times. This particular complicates the patient experience when you consider the particular medical condition they are already living with.  

In the pharma industry, we are focusing on solving this problem from our side – that is, creating systems that make it easier designed for patients to receive customized medicine.  

At Lonza, we address these challenges by automating the otherwise manual manufacturing process and bringing the manufacturing closer to the point of treatment. Lonza’s Cocoon platform is an automated patient-scale cell treatment manufacturing system that aims to boost access to life-saving cell-based therapies. The platform is improving access in order to personalized medicines by production therapies on-site at private hospitals in the point of care. The cell processing device can make treatments for a variety of illnesses and speeds up treatment timelines by reducing the vein-to-vein time to just 10 days.    

How far is the industry from fully automating the particular manufacturing process for cellular and gene therapies?

The particular successes in the cell therapy field have led in order to rapid growth within the number of healing strategies that are transitioning from the laboratory into the clinic. Despite this progress, there are still challenges to implementing completely automated manufacturing processes that will enable efficient clinical plus commercial deployment of novel therapies. Because different cell therapy developers require various processes, ideal automation platforms will need to be customizable and able to support a range of procedure steps plus conditions. Moreover, considerations regarding commercial scale needs and scale-up or scale-out strategies will be important to ensure the development of systems that can support commercially-viable processes.  

Though there has already been great momentum, automated production technologies continue to develop to tackle the needs inside the field, and we anticipate that in the next few years, all of us will see a refinement in standalone and integrated platforms that will enhance processing efficiency and drive the cost of goods down. These types of developments, in turn, will contribute to expanding the implementation associated with fully automated cell plus gene treatment manufacturing platforms.

What are usually some of the biggest challenges in order to tackle within the coming years?

Choosing the right format for a biologic is critical. The more complex the particular format will be, the more challenging it will be to choose the right protein engineering technology, cell line development, process optimization and development. In addition, the particular analytics to evaluate the product must be adapted or developed from scratch.  

Specifically in order to cell remedies, the field is progressing toward integrating in-process analytics to refine process advancement and make sure that critical quality attributes are achieved in the final product. Technology developers will need to integrate solutions within automatic platforms in order to enable these types of capabilities to address this need.

What advice would a person give to new startups planning to create these newer modalities of therapies?

My advice would be to choose an established CDMO partner to help the clinical and commercial manufacture associated with these brand new modalities. An experienced partner like a CDMO will have decades of expertise in developing biologics and will likely possess the encounter to overcome common growth and manufacturing problems as well as the mitigation or even de-risking procedures to solve them quickly and appropriately.   Within addition, an experienced CDMO should have the capabilities to advise and resolve increasingly complicated development plus manufacturing difficulties.

Likewise, when choosing a CDMO partner, become diligent. Ensure that they are factoring risk mitigation in to their timelines. If these people are encouraging manufacturing timelines shorter than industry standards, they might compromise your molecule’s manufacturability, safety or critical quality attributes. As most biologics fail in first-in-human trials, de-risking the early stages associated with development can lead to the re-engineering of that molecule or even a different lead candidate selected, which can save time and resources.