A View On - Lonza Podcast

EPISODE 7: Mid-season wrap-up

Season three so far, we’ve covered a lot!

In this summary episode, A View On host Martina Hestericova shares a secret and goes over a selection of the best ideas from season three so far.

The production team for A View On has managed to keep things moving along smoothly, so you most likely didn’t even notice that Martina was away for four months. She’s back! Listen in as Martina navigates us through a curated selection of the finest moments from the season: from cell culture to highly potent molecules, from inhalants to gene therapies, we’ve covered a lot this season.

Check out this summary episode and stay tuned for future topics such as antibody based therapies, health ingredients, and even forensic science.

Past Episodes

EPISODE 6: CAR-T Therapies

CAR-T Cell Therapy: Re-engineering the Immune System in the Fight Against Cancer

In this episode, Tamara Laskowski, Senior Director of Clinical Development in Personalized Medicine at Lonza, and Aya Jakobovits, from Adicet Bio, discuss the therapeutic potential of CAR-T cell therapy.

CAR-T cell therapy has generated immense enthusiasm within the oncology community since the first FDA approval in 2017. Currently, there are six commercially approved CAR-T cell-based therapies, with more on the horizon. These therapies have exhibited remarkable efficacy, particularly for patients who have exhausted standard treatment options. Industry experts Tamara Laskowski and Aya Jakobovits attest to the astounding outcomes witnessed in patients, some of whom have remained in remission for a decade after having received a CAR-T infusion.

CAR-T cells are modified white blood cells that are introduced into a patient’s body. These remarkable cells are meticulously engineered to possess synthetic receptors, known as CARs, which enable them to first identify then eradicate malignant cells with precision. By targeting cancer cells that exhibit a specific target antigen, CAR T-cells have the extraordinary ability to seek out and eliminate harmful cells, offering new hope in the battle against this devastating disease.

Curious to Know More?

Join us on this podcast episode as we explore the therapeutic potential of CAR-T cells, their path to clinical trials, and their role in providing astonishing outcomes for patients with limited treatment options.

KEY TERMS:

Highly Potent Active Pharmaceutical Ingredients (HPAPIs) are compounds used in the production of drugs that have high potency and therefore require special handling and containment due to their toxicity and potential adverse effects.

The STOP principle is an acronym that stands for Substitution, Technical measures, Organizational measures, and Personal Protective Equipment. It defines a hierarchy of protective measures to be implemented in the workplace, with personal protective equipment being the last resort when other measures are neither feasible nor effective.

Engineering controls are measures and systems implemented in the manufacturing process to minimize the potential for exposure to hazardous substances, such as HPAPIs. They include technologies, equipment design, and process modifications that help protect workers.

Personal Protective Equipment (PPE) is specialized gear and clothing worn by workers to protect themselves from potential hazards in the workplace. PPE is considered the last line of defense and should only be relied on when other control measures are insufficient.

Containment refers to the measures taken to confine and control highly potent compounds within the manufacturing process. Containment aims to minimize the release and exposure of these substances to ensure the safety of workers and the environment. It involves various engineering controls, procedures, and equipment to prevent contamination and maintain a safe working environment.

EPISODE 5: Highly Potent Compounds

Exploring Manufacturing and Market Trends in Highly Potent Compounds

In this episode, two Lonza experts, Managing Toxicologist Selene Araya and Charles Johnson, the Senior Director of Small Molecule Commercial Development, delve into the manufacturing process, trends, and future of highly potent compounds.

In the world of pharmaceuticals, some molecules possess an extraordinary level of potency. Known as highly potent compounds or HPAPIs, these substances have the remarkable ability to elicit a biological response in our bodies even at incredibly low doses—and they may even be the future of sustainable pharmaceuticals. Their potency enables targeted treatment of specific cell populations and often offers cost advantages in manufacturing. However, the production of highly potent compounds can create dangerous reactions and therefore comes with inherent risks for scientists and manufacturing personnel.

In this wide-ranging conversation about these powerful molecules, two in-house experts explore Lonza’s facilities and proficiency for the production of highly potent compounds, as well as the advantages of HPAPIs in different therapies. With Lonza’s extensive operating range, new safety challenges come up at each phase, whether it be small-scale lab operations or large-scale multi-ton batch manufacturing. Systematic approaches to protective measures ensure the safety of the staff, making sure to anticipate risks well in advance, and only relying on protective equipment as a last resort.

Curious to Know More?

Join us on this podcast episode as we explore the power and potential of highly potent compounds, delve into the challenges faced in their manufacturing, and envision a future where these compounds shape the landscape of sustainable pharmaceuticals.

KEY TERMS:

EPISODE 4: Injectable Delivery Devices

The Future of Injectable Medical Devices and Their Impact on Patient Care and the Environment

In this episode, Ian Thomson, the Vice President of Business Development at Ypsomed, and Roman Matthäs, Lonza’s Associate Director of Pharmaceutical Services, discuss the market trends in injectable delivery devices, how these devices are manufactured, and their future in contributing to sustainable pharma.

For decades, patients have been using self-administration devices to deliver medications through subcutaneous injections, with the insulin pen injector as perhaps the most well-known of these devices. Recent developments in drug delivery and device technology are significantly expanding the market. To fully leverage this opportunity for the benefit of both patients and the industry, manufacturers are now embracing a comprehensive product development strategy that integrates medical device development from the outset. This exciting convergence of newly available therapies and innovative at-home delivery systems promises to improve patient quality of life and health, with far-reaching social and environmental benefits.

When these delivery options are available, patients no longer need to visit hospitals or clinics for injections, which saves time and money while reducing the risk of infections. Injectable devices can be self-administered in the comfort of the patient's home. They also allow for precise dosing, which is particularly important for patients who require frequent treatment.

Curious to Know More?

Listen to this episode of A View On: Injectable Medical Devices to explore how self-administered medical devices are manufactured and get an inside look into the future market trends from industry experts Ian Thomson (Ypsomed) and Roman Matthäs (Lonza).

KEY TERMS:

Cell therapy is a medical treatment that introduces living cells into a patient's body to replace or repair damaged or diseased cells, thereby providing highly personalized therapy.

Gene therapy is a cutting-edge, targeted medical treatment that introduces genetic material into patient's cells to treat or prevent diseases caused by genetic mutations.

Autologous refers to cells, tissues, or organs that are derived from the patient, thereby providing highly personalized treatment.

Allogenic refers to cells, tissues, or organs that are derived from a donor but not from the patient himself, thus providing an alternative source of treatment.

Viral vectors are a powerful tool in gene therapy, where a virus is genetically modified to carry therapeutic genetic material into patient's cells, acting as a delivery vehicle for the therapy.

A Bioreactor is a sophisticated device or system used to grow cells or tissues in a controlled environment, often used in manufacturing cell and gene therapies. Automation has been shown to increase the final product's efficiency, consistency and quality, including cell and gene therapy manufacturing.

EPISODE 3: Manufacturing Cell and Gene Therapies

Scaling Up Cell and Gene Therapies: Automation Is the Next Step

In this episode, we take a deep dive into manufacturing cell and gene therapies with Lonza expert Behnam Ahmadian Baghbaderani, executive director of Cell and Gene Therapy Process Development.

Cell and gene therapies have the potential to revolutionize the treatment of rare genetic diseases, cancer, and neurodegenerative disorders. These therapies involve extracting cells or genetic material from a patient or donor, altering them and then re-injecting them back into the patient to provide a highly personalized treatment. However, the manufacturing process for these therapies is complex and expensive. To increase the availability of these therapies, the industry is making strides in scaling up the manufacturing process to reduce costs.

According to Behnam Ahmadian Baghbaderani, executive director of Cell and Gene Therapy Process Development at Lonza, “It is important to incorporate innovative technologies and reduce the cost of goods and production in order to make these therapies widely accessible for a large number of patients.”

One essential way to achieve this is through automation: automated cell culture systems, including bioreactors, can be used to grow and expand cells in a controlled environment, which reduces the need for manual labor while increasing consistency and reproducibility. Simply put, scaling up the manufacturing process using automation makes these therapies more widely accessible to the large number of patients who need them.

Curious to Know More?

Listen to this episode of A View On Cell and Gene Therapies to explore how cell and gene therapies are manufactured. Get an inside look into the next steps for the industry from Lonza expert Behnam Ahmadian Baghbaderani.

KEY TERMS:

Cell therapy is a medical treatment that introduces living cells into a patient's body to replace or repair damaged or diseased cells, thereby providing highly personalized therapy.

Gene therapy is a cutting-edge, targeted medical treatment that introduces genetic material into patient's cells to treat or prevent diseases caused by genetic mutations.

Autologous refers to cells, tissues, or organs that are derived from the patient, thereby providing highly personalized treatment.

Allogenic refers to cells, tissues, or organs that are derived from a donor but not from the patient himself, thus providing an alternative source of treatment.

Viral vectors are a powerful tool in gene therapy, where a virus is genetically modified to carry therapeutic genetic material into patient's cells, acting as a delivery vehicle for the therapy.

EPISODE 2: Manufacturing Inhaled Drug Products

What If the Jab Were a Puff? A Look at Drug Delivery to the Lungs

In this episode we explore the advantages of using inhalers for drug delivery with Lonza experts Kim Shepard and Matt Ferguson.

In late 2022, China introduced the world’s first Covid-19 vaccine to be inhaled into the lungs. The Chinese scientists who developed the vaccine tout its ability to directly stimu-late the immune system’s first line of defence – the lungs’ mucous membrane. However, vaccines are just the tip of the inhaler iceberg. While we all are familiar with metered-dose inhalers, as well as nebulizers, for asthma, a whole range of therapeutic options for many diseases are becoming available through the technology known as dry-powder in-halers, or DPI.

While the first commercially available DPIs appeared in the seventies, recent advances have opened the door to treatments for diabetes and even cancer. As with the Covid-19 vaccine, direct delivery to the lungs can be more efficient, but it also has the advantage of lowering toxicity by bypassing the liver altogether. Still, getting the correct amount of the molecule to the right part of the lung without unwanted immune responses is tricky business. Recently developed manufacturing techniques and new types of molecules make drug inhalers a continually evolving field full of potential advantages for patients.

Curious to Know More?

Listen to this episode of A View On, Manufacturing Inhaled Drug Products to learn more about what it takes to develop effective treatments with insights from Lonza’s Associate Director, R&D, Kim Shepard and Matt Ferguson, Lonza’s Head of Respiratory Drug De-livery.

KEY TERMS:

Inhalers are medical devices that deliver drugs to the lungs and take three principal forms: Nebulizers, which get their name from using a liquid mist, or nebula, to transport the drug to the lungs via liquid aerosol; . Metered dose inhalers are portable devices which use a propellant to administer a “puff” of drug to the lungs. Dry-powder inhalers use a dry powder that is driven by a patient’s own breath into the lungs with a sharp inhalation.

Excipients are substances that accompany the active pharmaceutical ingredient in drug delivery. For DPIs, they can be used to modify the density and shape of the powder’s molecules for more precise delivery as well as to improve stability and shelf life.

Spray-drying is a technique to engineer the shape and size of particles by dissolving the drug and excipients in a solvent and then converting the solution to a powder. In DPI manufacturing, spray-drying is a superior method to milling a molecule because it creates a specifically designed aerodynamic shape that is conducive to getting the molecule deeper into the lungs.

A granuloma is an inflamed area of the lung that is part of its natural immune defence and can be an unwanted reaction to administering a drug through inhalation. Proper drug formulation through computer modelling and toxicity studies, along with novel tech-niques such as spray-drying, can greatly improve a patient’s chances of avoiding granulo-mas and other unwanted immune responses.

EPISODE 1: Cell Culture Media

We are back! And in the first episode of our new season, we explore growing cells for therapeutic purposes with Lonza specialists Alexis Bossie, Director of Media R&D, and Tariq Haq, Senior Director of Global Media Marketing.

Lab-grown meat is having a moment—the FDA just declared one company’s culti-vated chicken safe to eat, and another type of lab poultry was just served for dinner to delegates at this year’s COP27 climate conference in Egypt. Whether this piques your pallet’s curiosity or turns your stomach, one thing is clear: growing meat in a lab for human consumption will take massive amounts of cell media.

What is cell culture media? It is the medium in which cells grow in a lab, serving as both the cell’s food and its shelter. The medium can take various forms, depending on which cell type is being grown and for what specific purpose. It is a careful re-cipe that balances the complex needs of cells in nutrients, energy, pH balance and saline percentage. Like our bodies, cell culture media is mostly water. However, crafting the right media is no simple matter: choosing the correct formula can make all the difference for the cell growth outcome, whether trying to stimulate virus pro-duction or make the tastiest animal-free cultivated cordon bleu on the planet.

Curious to Know More?

Listen to this episode of A View On, On to learn more about what it takes to grow cells in a lab. As a bonus for our listen-ers, at the end of the discussion, Alexis Bossie shares insights into the possibilities and obstacles of growing meat in the lab.

KEY TERMS:

Cell culture media is the medium in which cells grow. It must meet all environmental conditions to keep a cell alive and flourishing. Either as a liquid or gel, synthetic or organic, the cell culture media’s most important function is to deliver nutrients to cells and to wash away waste products.

The osmotic balance in cell media is the salt and water balance needed to maintain proper cell functio-ning. An imbalance creates uneven flows of water between a cell and its media, resulting in a cell burst or cell shrinkage.

A protein factory is a name given to batches of cells cultivated in a laboratory to produce high quanti-ties of one or several types of proteins, often for therapeutic purposes. It must not be confused with the cell’s own protein factory, aka the ribosome.

Limulus Amebocyte Lysate (LAL) is an aqueous extract of blood cells (amoebocytes) from the horseshoe crab, Limulus Polyphemus, that enables batch testing of vaccines and other drugs for endotoxins. The crab’s extracted blood is a surprising blue color due to the crabs’ copper-based Hamasyan. The obtained LAL is an opaque white-colored liquid that clots in the presence of any toxicity.

The metabolomics and the proteomics are the biological disciplines describing the metabolites and proteins in a cell. As these fields advance, so does the understanding of cultivating cells and developing the correct media for each type of desired growth and out-come.

Highlights of the second season of A View On, the Lonza podcast

Join us in celebrating the finale of our second season of A View On, the Lonza podcast.

Over the past few months, we have brought you a series of insider conversations with our experts at Lonza, our partners, and leaders in the industry exploring the new pharma and biotechnology trends. We explored exciting topics, such as oncolytic viruses, the human microbiome, antibody-drug conjugates, nuances of early drug development, capsule manufacturing, and the use of artificial intelligence in the pharma industry.

In the latest episode, the podcast host, Lonza’s Martina Ribar Hestericová, recaps the highlights from this season and looks forward to later this year for what is coming up in the next season.

EPISODE 10: Artificial Intelligence and Life Sciences: The Dawning of a Digital Revolution in Pharma Manufacturing

Dr. Loubna Bouarfa, CEO of OKRA.ai, and Stephan Rosenberger, Lonza's Head of Digital Transformation, discuss how AI is currently transforming the pharma industry.

Machine learning is an essential subset of the vast field of Artificial Intelligence, in which computer programs aim to mimic human intelligence. Machine learning is at work in many of the algorithms that impact our daily lives, from suggesting new songs we might like to targeting ads. These algorithms learn from large data sets similarly to how a child learns during the early stages of development. As the algorithm matures from child to teenager to adult, it refines its own functioning by learning from its errors and through help from humans, much like we do.

This powerful way of programming is making tsunamis across nearly all industries. It notably transforms the pharmaceutical world from drug discovery to production and even sales. Whether it is creating AI brains for companies to build digital workers to help their human employees or streamlining the factory with ultra-reliable predictive maintenance, the machine learning and artificial intelligence revolution is well underway.

Curious to Know More?

Listen to the conversation between A View On host Martina Hestericová and two world specialists about the present and future applications of AI and Machine Learning in the pharmaceutical industry.

KEY TERMS:

Artificial Intelligence is a field of computer science where simulations of human intelligence by computer processes are used to improve the performance of machines.

Machine Learning is a subset within the field of AI that is inspired by the way humans learn. Computational programs in the form of algorithms continually evolve by "learning" or processing information through trial and error, often with the help of human intervention. The goal of machine learning is to create machines that are independent learners capable of solving problems without human involvement.

An AI brain, or digital brain is the term used by OKRA CEO Dr. Lubna Bouarfa to describe a form of AI that learns from several data sets to create a company-specific intelligence to aid decision-making and predictions. For Bouarfa, the company's product can be employed to solve many of the current bottlenecks and problems in Life Sciences and pharma.

Synthetic route optimization is used to map out the best way that a scientist can synthesize a compound. With the help of machine learning and AI, this route can be even further optimized by harnessing vast data sets and predicting outcomes. It is only one of many avenues where AI can greatly improve the efficiency of existing technologies in pharma manufacturing.

In edge computing the computational work happens outside of the cloud and closer to the actual data event, which allows for real-time processing. With bigger data sets needed to feed in-house AI systems, edge computing architecture holds many advantages for companies looking to harness the power of AI for functions such as automation and safety.

EPISODE 9: Where There’s A Risk, There’s A Way: De-risking Drug Development at the Earliest Stages

Lonza’s wide array of analytical tools and professional experience create a go-to solution for small biotechs looking to decrease risk in their drug development process.

A successful drug can easily take up to 15 years and cost over 2 billion US dollars to de-velop. Considering that nine out of ten drug candidates fail in clinical trials, companies are incentivized to reduce the risk of drug attrition at the earliest stages of development. Many of the drugs currently in the manufacturing process around the world are initially developed by small biotech companies—companies that often do not have the tools and experience necessary to assess the risks of developing their therapeutic drug can-didates properly. This is where Lonza’s Early Development Services steps in, headed by today’s guest Raymond Donninger.

To start the de-risking process, Donninger and his team employ the latest computer modeling tools to predict how the molecule will react with a human body. And while these in silico tools are very powerful, several other steps are needed to fully assess risk potential, including novel cell-based assays and a full economic viability appraisal. The de-risking process is highly technical and relies on years of research experience since no novel algorithm or new in vivo testing technique—regardless of its power—can fully replace the analytical acuity of the human brain combined with decades of market know-how.

Curious to Know More?

We previously addressed the importance of immunogenicity in decreasing risk in drug production in Episode 5. To take an even deeper dive into the whole process, listen to the conversation between Martina Hestericová and Raymond Donninger, the Senior Di-rector of Commercial Development for Lonza’s Early Development Services.

KEY TERMS:

In silico vs. human cell in vitro assays are two essential ways to test a molecule’s safety and market viability. In silico tests run computer models to assess a molecule’s interaction with, for example, a human immune system; conversely, in vitro testing assesses the molecule’s interactions with cells and even human cell tissue.

Wanted attrition occurs when it reaches clinical trials but fails for one reason or another. According to Donninger, an attrition rate of nine out of ten candidates has remained stubbornly high over the years.

The dip molding process is when a drug candidate fails because even though the science looks good, the molecule would be inescapably harmful to humans. Unwanted attrition happens when a molecule has true therapeutic potential but is not developed properly. The de-risking process addresses unwanted attrition to improve the chances for viable and safe therapies to make it to market.

EPISODE 8: Capsule Manufacturing: It’s Not Only What’s Inside That Counts

The recent EU ban on Titanium Dioxide and changing customer habits are shaking up capsule production.

Over the past few years, the coloring and manufacturing of pill capsules have undergone significant changes due to new EU regulations and customer demand for natural ingredients. And while originally invented to mask and protect the contents inside a capsule, research suggests that the color of a tablet or pill can affect how patients feel about their medication.

Until recently, manufacturers have primarily used Titanium Dioxide (TiO2) to create white capsules due to its efficiency in protecting the active ingredients from UV rays. However, this year an EU-wide ban on TiO2 has forced the industry to move towards alternatives that work as well, or better, than TiO2. To add to the colorant shake-up, many people are actively avoiding unnatural ingredients in their food and nutritional supplements, which has created a new demand for plant-based capsule colorants. Anticipating these changes and solving the technological challenges in a timely manner are key to a successful long-term strategy for capsule manufacturing.

Curious to Know More?

Listen to the conversation between A View On host Martina Hestericová and Ljiljana Palangetic, Lonza’s Associate Director of Hard Capsules R&D, about the challenges and solutions in current capsule manufacturing.

KEY TERMS:

Pharmaceutical capsules can be either hard or soft. Soft-shelled capsules are one unique mold that encapsulates the contents, whereas the more widely-used hard-shelled capsules—such as the ones produced by Lonza—are two molded telescopic pieces of capsule: a smaller one contains the active ingredients, and a larger one encloses the capsule.

Titanium dioxide (TiO2) is a widely-used pigment in capsule manufacturing, as well as in food, paint and sunscreen. Considered completely inorganic and nontoxic from a chemical point of view, it is labeled as an unnatural ingredient for ingestion, and carries the E number E171. Earlier this year, the European Food Safety Authority (EFSA) announced a six-month phasing-out ban of the colorant over concerns about nano-sized particles of TiO2 accumulating in the body. The full ban takes effect in August.

The dip molding process is the manufacturing process for capsules. The final shape of the two pieces that make the capsules is defined by specifically designed molds, which are dipped in a bath of liquid formulation to pick up material that will, after the drying process, give the final capsule form, shape and composition.

EPISODE 7: Antibody-Drug Conjugates: Next Generation of Targeted Cancer Treatements

Iwan Bertholjotti and Lawrence Bonnafoux from Lonza give an insider look at how these promising treatments make it from development to commercialization.

Chemotherapy is the first-line treatment for most types of cancer. However, one of the major challenges with this approach is that it targets both cancer and healthy cells, with patients suffering severe side effects. A new class of therapies, called antibody-drug conjugates, or ADCs, can target tumors much more precisely by harnessing the power of antibodies. The antibody can bind specific types of tumor cells, delivering a fatal blow to the cancer cells while sparing healthy cells. These promising new drugs have seen a significant uptick in FDA approvals in recent years, pointing towards a trend that could transform the way many diseases are treated.

While numerous companies succeed in developing promising ADCs, manufacturing such complex and highly potent treatments presents unique challenges. The intricacy of scaling up the manufacturing of ADCs leads many companies to outsource their production, and Lonza currently fabricates the majority of ADC therapeutics in the world. For the companies that choose to work with Lonza, the collaboration simplifies the process and streamlines the supply chain. Decades of collective experience in fabricating ADCs means that the drugs make it from discovery to approval in less time, improving patients' lives through more effective, targeted treatments with fewer side effects.

Curious to Know More?

Listen to the conversation between A View On host Martina Hestericová and two of Lonza’s experts on ADC manufacturing—Lonza’s senior director of Commercial Development of bioconjugates, Iwan Betholjotti, and Lawrence Bonnafoux, Lonza’s Head of MSAT BioConjugates.

KEY TERMS:

Bioconjugates are a class of biopharmaceuticals developed by attaching two molecules together, of which at least one is a biomolecule. Examples of bioconjugates include antibody-drug conjugates (ADCs), PEGylated proteins, and vaccine conjugates.

Antibody-drug conjugates consist of three parts: an antibody, a cytotoxic drug and the linker that covalently binds these two together. This approach combines the targeted delivery of the antibody with the cancer-killing power of the cytotoxic drug that would be too potent to be used on its own.

A cytotoxic drug is a drug that contains a molecule toxic to cells, leading to cellular death. Used in traditional chemotherapy, these molecules attack both healthy and cancerous cells. When linked to an ADC antibody, they target only the tumor.

Targeted delivery of a cytotoxin is when a cell-killing toxin is delivered to a specific type of cell, such as tumor cells. This specificity allows for effective cancer treatment with fewer unwanted side effects for the patient.

EPISODE 6: Manufacturing of Exosomes

Putting Manufacturing First: Codiak Moves Swiftly into Clinical Trials with Exosome-based Treatments

Sriram Sathyanarayanan, Codiak’s CSO, and Linda Bain, their CFO, share how the company moved into clinical trials in under 6 years.

Exosomes, extremely small vesicles shed by all cell types, promise to become a viable delivery system for treatments of many diseases. But until recently, manufacturing them at a commercially viable scale has been unfeasible. That is why in 2015 the company Codiak took a two-pronged approach to developing exosome-based treatments: prioritizing both the engineering and manufacturing tracks from the outset. A mere six years after the company was launched, this approach has proven effective, with two promising studies in the clinic for tumor treatments, while most other developers are still at the starting blocks.

The exosome field today holds the kind of promise that antibody and protein-based therapeutics did in the 1980s—the potential to improve both treatments and patient well-being is great. With a low risk of immunotoxicity, leveraging their natural abilities and engineering them to deliver targeted therapies could open new therapeutic pathways to previously undruggable targets. Yet as recently as only a couple of years ago, manufacturing exosomes was limited to small batches. Codiak has successfully increased production to thousand-liter batches, permitting clinical studies and greatly improving the prospective of widespread use. In collaboration with Lonza, Codiak is doubling down on their advantage with a recently established Center of Excellence for exosome manufacturing in Massachusetts.

To learn more about Codiak’s pipeline of therapeutic candidates with a potential to transform patients’ lives, visit: https://www.codiakbio.com/pipeline-programs/pipeline

Curious to Know More?

Listen to Martina Hestericová’s conversation with Sriram Sathyanarayanan and Linda Bain as they discuss the advantages of exosome treatments, how they are developed and why the company’s early manufacturing strategy is paying off.

KEY TERMS:

Exosomes are nano-sized delivery vehicles generated by all eukaryotic cells. They are roughly between 30 and 120 nanometers large and originate when endosomes, or intercellular vesicles, are released into the blood, milk or tissue. Exosomes then become messengers and surrogates for the original cell. Their surface markers represent a location code and spread through the extracellular space in the body to communicate with other cells and deliver packages.

Commercial exosome manufacturing is the scaling-up process of moving from small-batch exosome production that uses ultracentrifuges to large-scale production that in many ways resembles the processes already used to manufacture antibody and protein-based therapies.

The exosome’s lumen is the interior volume of the exosome where, through biological engineering, the therapeutic molecule can be placed. The molecule can also be on the surface of the exosome, allowing for two alternative payload capacities, depending on the target.

Immunosafety and immunotoxicity refer to how potentially safe or toxic the immune system’s reaction to a molecule may be. Since exosomes already have a history of low immunotoxicity – think of blood transfers – their immunosafety is already proven to be very high.

EPISODE 5: Importance of Immunogenicity

De-risking Drug Development: Early Testing for Toxicity Saves Time and Resources

Yvette Stallwood, head of Lonza’s Early Development Services, talks about patient safety and other advantages of early testing for immunogenicity in the drug development pipeline.

In the high-stakes drug discovery game, from IND filings all the way up through the clinical trial phase, regulatory authorities are now expecting developers to have an immunogenicity risk strategy in place. “It really is essential that drug developers assess the immunogenicity risk as early as possible in the pipeline, as not only can it impact the functionality of the drug, but it can also be a significant safety risk for the patient,” explains Yvette Stallwood, whose work at Lonza’s Early Development Services (EDS) is helping small and large biotech companies reduce risk with a “Right First Time” approach when developing drug therapies.

Drug candidates often fail during clinical trials due to their toxicity to patients, which is evident, for example, in an immunogenic reaction—where the drug triggers an unwanted immune response known as immunotoxicity. This can result in the loss of years of work and funding. Stallwood and her team encourage their clients to begin with in-silico testing, where up to a thousand digital models of potential immunoresponses can be predicted. Once the digital models show a candidate to have a low risk of toxicity, the EDS team then moves to human donor cell assays—with the advantage of screening up to fifty different immunotypes. The ideal time to assess immunosafety and immunotoxicity is well before deciding on a molecule as a lead drug candidate. By understanding as much as possible about the potential product through early testing, biotech companies are better equipped to take the correct path to regulatory approval with a drug that is ultimately safer for patients.

Curious to Know More?

Listen to the conversation between A View On host Martina Hestericová and Lonza’s head of EDS Yvette Stallwood as they discuss de-risking the drug development process.

KEY TERMS:

Host and Health: Tailoring Personalized Medicine Using The Unique Microbiome Fingerprint

Professor Eran Elinav from the Weizmann Institute of Science discusses how the interaction between the microbiome and its host is transforming personalized medicine.

I believe that in the next five to ten years, exploiting the potential of the microbiome will be central to personalized and precision medicine,” explains eran elinav. his research into this second genome in the human body at the weizmann institute of science in isreal is shedding light how these trillions of cells function and interact with their host. the individualized data from the unique microbiome fingerprint can be harnessed to tailor nutritional therapies to improve metabolic functions in the treatment of, for example, obesity and type 2 diabetes—with a wide range of further potential applications. and even small molecules found within the microbiome could themselves be developed into drugs. the future hope lies in the inherent therapeutic translatability of these insights from host-microbiome interaction research into treating the whole spectrum of metabolic

Curious to Know More?

Listen to the conversation between Lonza’s Martina Hestericová and Weizmann Institute of Science Professor and researcher Eran Elinav in this special episode of the "A View On" podcast.

KEY TERMS:

Genome: All of the genetic information of an organism. When speaking about the microbiome, it refers to an entirely different organism that is comprised of its own genetic makeup from the host—the interaction between the two genomes is the subject of study known as host-microbiome interaction.

Microbiome: The extremely diverse ecosystem of hundreds, sometimes thousands of different species of microbes found in and on the human body. Microbial biodiversity is key to a healthy microbiome and a poor microbiome is linked to diseases such as inflammatory bowel disease, cancer and possibly some central nervous disorders.

Therapeutic translatability: The ability to translate or apply basic research into therapies for the benefit of humans. As we understand more how the complex microbiome works, Professor Elinav asserts that these insights translate directly into ways to manipulate it and improve health.

Personalised or Precision Medicine: A general trend to adapt treatments to individuals instead of a one-size-fits-all approach. In the context of host-microbiome research, as the microbiome is unique to each individual, it could hold the keys to specialized treatments by harnessing the individualized data.

Bridging Business and Biotechnology: Kodiak Sciences Is Increasing Treatment Efficacy for Retinal Diseases

Victor Perlroth, MD, the Chairman and CEO of Kodiak Sciences, discusses how the company’s ABC platform medicines are designed to treat the leading causes of blindness.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in adults worldwide. This disease deteriorates the macula, a miraculous little spot on your retina that allows for precise vision in good light. Although several treatments exist for macular deterioration, they require frequent trips to the doctor’s office for uncomfortable but quick and routine injections directly into the eye. The required frequency of the treatments means that most patients miss appointments, leading to undertreatment of the disease and permanent vision loss. In a manufacturing collaboration with Lonza, Kodiak is designing novel antibody-biopolymer conjugate (or ABC) medicines with the same efficacy and safety with much longer durability, allowing patients to visit the doctor on a realistic schedule over the long term. By focusing on business implementation alongside formidable biotech R&D, Kodiak Sciences is on track to bring together the necessary clinical and manufacturing elements for an FDA filing in 2023.

Curious to Know More?

In this most recent episode of “A View On,” Lonza’s Martina Hestericová is joined by Victor Perlroth, MD, the co-founder and CEO of Kodiak Sciences, to talk about the recent developments in AMD treatment research.

KEY TERMS:

Age-related macular degeneration (AMD) is a common degenerative disease of the retina. There are two types of AMD:

Dry AMD occurs when the formation of debris (drusen) on the retina causes the macula to deteriorate over time. Patients sometimes experience vision loss and frequently experience substantial functional limitations, including vision fluctuations, loss of peripheral vision, and reduced night vision.

Wet AMD is an advanced form of AMD. While wet AMD represents only 10% of the number of cases of AMD overall, it is responsible for 90% of AMD-related cases of severe vision loss. Wet AMD occurs when the growth of abnormal blood vessels underneath the macula leads to leakage of fluid and blood, which leads to visual distortion, acute vision loss, and total blindness if left untreated.

Vascular endothelial growth factor (VEGF) is a sub-family of factors that stimulate the growth of blood vessels. In the case of AMD, these VEGF are overexpressed, creating leaking in the macula. This leakiness causes fluid to exit from blood vessels, causing swelling – or edema – of the retina and loss of vision.

An antibody-biopolymer conjugate (ABC) is Kodiak Science’s proprietary platform for designing and developing drugs into the retina. The antibody in the KSI-301 molecule inhibits VEGF, while the biopolymer is comprised of phosphorylcholine, which creates a sort of “water cloak” around the antibody to increase its effectiveness.

Phosphorylcholine is a natural component of the cell membrane of all the cells in our body, with remarkable properties. It attracts and binds water in a very strong – even permanent – way, creating what is known as “structured water,” which then impacts all biological interactions in the local area.

Episode 2: Horseshoe crabs and recombinant factor C

Safe Jabs Thanks to Horseshoe Crabs: Making Sure Your Injection is Free of Endotoxins

Allen Burgenson, Lonza’s expert for all things testing, speaks to us about the dangers of endotoxin contamination and the future of non-animal testing for it.

“Before testing for endotoxins in the 1940s, a physician literally had to gauge the risk to your life because of something called injection fever,” explains Allen Burgenson. Luckily, we’ve come a long way since then. Thanks to advanced testing methods, one can rest assured today that any sort of injection or implant is completely free of dangerous endotoxins. Currently, the predominant mode is Limulus Amebocyte Lysate (LAL) testing, in which scientists harvest the bright blue blood of American Horseshoe Crabs and use the animal’s primitive immune system to look for clotting reactions that would indicate the presence of any endotoxins. The horseshoe crabs, Burgenson explains, survive the extraction unscathed and are safely returned to the waters in less than 24 hours. However, in a continual attempt to remove animals from the testing pipeline, Lonza’s recombinant factor C assay known as PyroGene could eventually replace LAL testing.

Curious to Know More?

In Episode 2 of the new season of the podcast A View On, host Martina Ribarhestericova speaks with Lonza expert Allen Burgenson to discuss his close bond with the American Horseshoe Crab and the history of testing for endotoxin contamination.

KEY TERMS:

Endotoxins are parts of bacterial membranes that could lead to a harmful reaction – or even death – if they enter a patient’s bloodstream or spinal fluid. Surprisingly, we have kilograms of endotoxins in our stomachs, but even little more than a nanogram in the bloodstream could be deadly.

Bacterial endotoxin tests, or BETs, is the general name for all assays used to detect endotoxins.

Rabbit pyrogen tests are BETs that were developed in the 1940s using rabbits as test subjects. To ascertain the endotoxic danger to humans, the scientist observes a rabbit’s reaction to an injection over a period of 3 hours. The European Pharmacopoeia Commission decided in June 2021 to completely replace the rabbit pyrogen test (RPT) within approximately 5 years.

PyroGene recombinant factor C is an animal-free way to test for endotoxins. It was initially developed at the National University of Singapore by Lin Deng and her husband Bo Ho to save money on testing at their relatively small lab. Lonza collaborated with Deng and Ho to become the first company to offer the test on a commercial scale.

A Welcome Virus: Cracking the Viral Code for the Battle Against Cancer

Chairman and founder of PsiVac, Prof. Ghassan Alusi, and the chief operating officer, Imad Mardini, discuss how the company’s proprietary oncolytic virus platform offers new hope for cancer patients.

During a time when everyone actively fears viruses (especially THE virus) and their mutations, it is only cancer cells that have cause to worry about oncolytic viruses, and rightly so. These mutated viruses are administered directly into a tumor. Once inside, they crack open the tumor’s cells in a process known as lysing that provokes a strong response from the body’s immune system, which has, until then, ignored the cancerous cells. What’s more, the therapy’s attack doesn’t stop at a single tumor. The replicating and lysing viruses release previously hidden tumor-associated antigens (TAAs) that alert the immune system about cancer cells to attack all over the body. The body’s own immune system then goes on to destroy previously unrecognized tumors far removed from the initial injection point. The biotech company PsiVac advances this technology even further by creating a treatment platform that transforms the adenovirus, aka the common cold, into an especially powerful oncolytic virus. A precision modification in the virus’s DNA improves its efficiency against cancer cells while making it harmless to other cells, rendering the treatment at once more effective and safer for patients. “Now that the technologies of other forms of immunotherapy are gaining ground, and as cancer remains a major cause of mortality, we now understand there is a huge need for oncolytic viral therapy,” says Prof. Alusi, whose company has planned to start Phase 1 clinical trials later this year. Unlike other immunotherapies, such as patient-centric CAR T-cell therapy, oncolytic viruses can be made in relatively large quantities once their efficacy and safety have been proved.

Curious to Know More?
In the first episode of the new season of the podcast A View On, host Martina Ribar Hestericová discusses the current state of oncolytic viruses and their promising applications with Prof. Ghassan Alusi and Imad Mardini.

KEY TERMS:

Cell lysingis the process of breaking down a cell’s membrane, destroying the cell and releasing its contents into the body. If an oncolytic virus lyses a cell, it releases replicated versions of itself as well as antigens helpful in the immune system’s fight against a tumor.

Tumor-associated antigens (TAAs)are released once a cancer cell is lysed, setting the previously dormant immune system into action. The release of TAAs means that the tumor is no longer successfully hiding from the immune system, and the body can begin to fight the disease by its own means.

Bioink: A material composed of living cells and biopolymer gels that, once extruded by the printer, can be organised into tissues, organs, and organoids.

The cytotoxicity of a virusis the extent to which a virus attacks and destroys cells, often an undesirable event. However, with oncolytic viruses, this cytotoxicity works in a patient’s favor, thanks to gene editing, by being specifically designed to attack cancer cells.

An agnostic oncolytic virus targets not only one or a group of cancers but is effective against all malignant solid palpable tumors. PsiVac’s modified adenovirus has proven agnostic so far, making it a powerful weapon in the fight against cancer.

EPISODE 10: Phage Therapy

Devouring Bacteria: How Phage Therapy Is Shaping Antibacterial Treatments of the Future

In this episode we speak with the CEO of BiomX, Jonathan Solomon, about produc-ing and using phages to test and treat various diseases and conditions.

Until very recently, treating a condition such as acne with an army of microscopic bacteria-destroyers known as phages—bacterial viruses that target and kill specific bacteria—would have seemed highly unlikely. However new research linking acne to an imbalance in the skin’s microbiome has opened the door to innovative treatment approaches. That’s where the biotech company BiomX comes in. Uniting powerful computational science with the in-herent capacity of phages to destroy specific bacteria, BiomX creates natural and synthetic phage therapies for some of the most troublesome bacteria-related health issues: acne, atopic dermatitis, cystic fibrosis, inflammatory bowel disease (IBD) and even colorectal can-cer. For acne the company has developed a successful cocktail of three different phages to treat the condition, with phase 2 testing close on the horizon. BiomX’s developments in phage therapy promise to change the way we treat imbalances in our microbiome, with potential health benefits for large swaths of the population.

Curious to Know More?
To learn more about BiomX, listen to the conversation with Jonathan Solomon on this episode of A View On: Phage Therapy.

KEY TERMS:

Bacteriophage (also known as a phage): A virus that attacks and devours only bacteria (‘phagein’ in Ancient Greek means to devour). Bacteriophages are bacteria-specific, which is both an advantage and disadvantage in manufacturing treatments. Fun fact: taken altogether, bacteriophages are the most numerous entity on the planet.

Phage cocktail: Since a phage targets and destroys only one type of bacteria, treatments for com-plex ailments necessitate a mixture, or cocktail, of different phages to be effective.

Phage fermentation: Although destructive, unwanted phages can grow during fermentation processes for wine-making and milk production, fermentation is nevertheless the optimal way to produce phages for therapeutic uses.

Computational (science): Computer modelling of the phage and its potential interaction with specific bacteria (known as in silico testing) allows researchers to develop phage cocktails more effi-ciently and with a greater chance of success.

EPISODE 9: Streamlining Cell and Gene Therapy Manufacturing

Delivering Personalized Therapies: Streamlining the Supply Chain for a New Generation of Treatments

In this episode, we speak with Amy DuRoss, Co-Founder and Chief Executive Officer of Vineti, about the challenges facing "just-in-time" manufacturing and delivery of personalized therapies—and the solutions her digital startup provides.

According to Amy DuRoss, the COVID-19 vaccine distribution has exposed existing deficiencies in the entire pharmaceutical supply chain. This situation echoes, albeit on a far smaller scale, the distribution complexities of delivering cell and gene therapies (CGT). Unlike more traditional treatments, CGT requires the extraction of live cells from a patient or donor to then be delivered to a manufacturer and make it back to the patient in a timely manner. Her company Vineti "introduces a new level of fidelity, control, and transparency" into the personalized drug delivery process, streamlining CGT distribution through a novel digital orchestration platform. Based on an astute understanding of the behavior of care providers, specialized couriers and CGT manufacturers, her company has developed a software infrastructure that supports this exponentially complex delivery process. By facilitating Good Manufacturing Principles for all required stakeholders in the advanced therapy process, the Vineti platform ensures regulatory compliance and maintains both Chain of Identity and Chain of Custody from cell collection to manufacturer and back to the patient.

Curious to Know More?
Take a listen to this episode of A View On: Streamlining Cell and Gene Therapy Manufacturing to learn more about Vineti. At the end of the discussion, as a bonus for our listeners, Amy DuRoss offers insight into some of the difficulties encountered in the COVID vaccine rollout, and how it parallels the complexity of the supply chain for CGT.

KEY TERMS:

Personalized medicine and therapies, such as cell and gene therapies (CGT), treat patients on a much more individualized basis. They require an unprecedented level of automation and navigation because the materials used to prepare the end product are raw cells originating from a donor or a patient.

Good Manufacturing Principles (or Practices), GMP for short, are practices that ensure adherence to the guidelines put forth by regulatory agencies. They apply to any manufacturing industry but reach an unparalleled level of complexity in CGT production due to the implication of health care providers in the cell extraction and donor matching processes.

A digital orchestration platform such as Vineti's uses the power of data management and user experience design to organize and execute an effective supply chain system in the face of exceptional complexity and strict regulations.

Chains of Identity and Custody in the pharmaceutical supply chain are the cornerstones of regulatory compliance, whereby each step in the process and each individual involved is transparently identifiable in order to reduce the risk of contamination and to eliminate fraud. With CGT production, the process of extracting the raw materials for the treatment directly from the patient or donor multiplies the Chains of Identity and Custody, exponentially increasing the supply chain complexity.

Exosomes Know Where To Go: Using the Body's Own Cell-to-Cell Communication Network for Diagnostics and Drug Delivery

We speak with Uwe Gottschalk, the Chief Scientific Officer of Lonza, about how a better understanding of exosomes is leading to new treatments and diagnostic technologies.

According to Uwe Gottschalk, the exosome revolution is already in full march. As researchers begin to identify how these cell-generated, nano-sized delivery drones function in the human body, novel drug delivery prospects are emerging, including applications for cancer, neurodegenerative diseases and spinal cord injury recovery. Perhaps even more exciting is the role exosomes will play in diagnostic applications in the near future, wherein a liquid biopsy, based on a blood sample, would detect cancer or other diseases both more easily and in a more timely fashion than traditional biopsies. One of the many challenges is the ongoing task of defining the manufacturing protocols and processes for this new biotechnological paradigm. Even so, the field is abuzz with new discoveries, trials and general optimism about the potential of these microscopic extracellular delivery vehicles.

Curious to Know More?
Lonza's Chief Scientific Officer gives us his expert insight into exosome research and application in this special, in-house episode of the podcast "A View On."

KEY TERMS:

Exosomes are nano-sized delivery vehicles generated by all eukaryotic cells. They are between roughly 30 and 120 nanometers large and originate when endosomes, or intercellular vesicles, are released into the blood, milk or tissue. They then become messengers and surrogates for the original cell. Their surface markers represent a location code and spread through the extracellular space in the body to communicate with other cells and deliver packages.

Extracellular vesicles (EV) are particles released from cells that cannot replicate but otherwise behave like the surrogate cells from which they originate. While there is some overlapping in definition between exosomes and EVs—all exosomes are extracellular vesicles but not vice-versa—exosomes are defined by their size (30 to 120 nm) and their biogenetic origin.

Liquid biopsy: As with a traditional biopsy, a liquid biopsy is a test to diagnose and monitor diseases that uses a blood sample instead of a tissue sample. As a liquid biopsy is not restricted to one tissue or part of the body, the test is less invasive, cheaper and even more precise.

Messenger RNA (mRNA) as a cancer biomarker: Recent research has proven that mRNA from a blood test can be analyzed to find cancerous and pre-cancerous tumors throughout the body. As exosomes transport and stabilize the otherwise highly unstable mRNA, they could be targets for early detection and treatment in the near future.

EPISODE 7: Bacthera

Bugs as Drugs: Harnessing the Therapeutic Potential of the Microbiome

Lukas Schüpbach, the CEO of Bacthera, and Gemma Henderson, Bacthera’s Head of Project and Portfolio Management, speak to Lonza about creating pharmaceuticals from the human microbiome.

The human microbiome, comprised of trillions of bacteria, fungi, viruses, and archaea, is unique to each individual and develops over the course of lifetime, stabilizing once we reach adulthood. Despite the widespread understanding that this microbiome is a key component to our health, there are currently no commercially available live biotherapeutic products (LBPs). There is, however, an increasing amount of scientific evidence that using live biotherapeutic products to promote a vigorous microbiome can improve general physical health and positively impact quality of life by targeting diseases such as obesity, diabetes, inflammatory bowel syndrome and cancer. The biopharma company Bacthera is manufacturing and testing these difficult-to-produce anaerobic bacteria treatments that could improve metabolic functions and have anti-inflammatory effects. Alongside manufacturing, Bacthera is meeting the challenging delivery process to harness the therapeutic potential of the microbiome through easily administered, encapsulated pills.

Curious to Know More?
Listen to the conversation between Lonza and Bacthera in this episode of the podcast "A View On."

KEY TERMS:

Microbiome: The extremely diverse ecosystem of hundreds, sometimes thousands of different species of microbes found in and on the human body. Microbial biodiversity is key to a healthy microbiome. A poor microbiome is linked to diseases such as inflammatory bowel disease, cancer and possibly some central nervous disorders.

Live biotherapeutic products: These pharmaceutical products, LBPs for short, are unique because their active substance is actually a living organism. that has been identified as showing promise in treating one or sometimes several diseases.

Enclosed process: The manufacturing of LBPs necessitates special equipment and expertise since many of the microorganisms are anaerobes and spore-forming organisms. To ensure a robust process with high yields, the manufacturing must be entirely enclosed so that these strains are not exposed to oxygen.

Entrinsic strict delivery: As some microbes would not make it to the intestine by way of stomach acids, Bacthera has access to a proprietary technology that encapsulates the microbe to ensure targeted and precise delivery.

EPISODE 6: Gene editing

Pioneering Precision: Cellectis Develops Immunotherapies for Genetic Diseases and Disorders Through Cutting-edge Gene Editing

André Choulika, the Chairman and CEO of Cellectis, talks to Lonza about the company's clinical trials of their revolutionary gene editing technology.

Since the arrival of Crispr in 2009, gene editing has made its way into labs across the globe, and its groundbreaking importance was further acknowledged through the 2020 Nobel Prize in Chemistry. Gene editing corrects within the DNA exactly as one edits a text: cutting, copying, replacing and deleting. Taking up the mantle of gene editing for medical treatments, the biopharmaceutical company Cellectis focuses their 20 years of experience on developing cancer immunotherapies. Safety through precision is the ultimate priority for Cellectis. The gene-editing company turns to Crispr for research but has found TALEN to be more precise in therapeutic uses. First, the gene cutter is introduced into a healthy donor T cell to destroy its receptor. This makes it blind so that the T cell doesn't attack the patient's cells (also known as graft versus host disease), and only the CAR carries the information about which cells to attack. The TALEN then travels to the cell via the CAR-T cell and cleaves the gene where it needs to be corrected. Cellectis has several products in the clinical trial stage that are based on allogenic gene-edited CAR-T cells: U CAR-T 22 for acute lymphoblastic leukemia, U CAR-T 123 for acute myeloid leukemia, and U CAR-CS1 for multiple myeloma.

Curious to Know More?
Cellectis CEO André Choulika explains the technology of allogenic gene editing they invented in this episode of the podcast "A View On."

KEY TERMS:

TALEN: Transcription Activator-Like Effector Nuclease, or a hybrid protein that is engineered to cut specific sequences of DNA

T cell: an immune cell that circulates in the body and recognizes any foreign body

CAR T cells: T cells engineered with a receptor protein for the purpose of targeting a specific protein on a cell. A CAR protein recognizes the antigen associated with the cancer cells and signals the T cell to fire at the cancer cell.

Allogenic gene therapy: donor T cells are genetically engineered to target a specific protein within the patient to attack the associated antigen of a gene mutation or genetic disease

EPISODE 5: Therapy administration and its safety

From Gene to Vial to Patient: Lonza Experts Run Biotech Products Through a Gauntlet of Real-world Simulations Before Release

Hanns-Christian Mahler, head of Lonza Drug Products Services, and Ahmed Besheer, head of formulation development 2, talk about how Lonza is leading the way in providing an essential service to clinical partners.

In the field of CDMO drug development, the new gold standard is end-to-end service, or bringing a pharmaceutical from gene to vial to patient. In 2016 Lonza established its Drug Product Services (DPS) to realize this supply chain model for its partners and clients. Since then the DPS has grown to a workforce of over 250 experienced experts focused on safety, efficacy and quality. They reduce complexity and improve regulatory compliance for Lonza’s clinical partners. To ensure that Lonza’s pharmaceuticals perform as expected in real-world situations, the DPS team simulates the entire administration process until certain the patient will receive the correct dose of the highest quality. Lonza works with clients around the world, making this service indispensable to international partners and colleagues in clinical practice, since clinical circumstances and regulations can vary greatly from country to country. The DPS’s results also contribute to the basic science that informs drug creation and delivery, offering the opportunity for Lonza researchers to publish and share their discoveries with the larger scientific community.

Curious to Know More?
Listen to the conversation with Lonza researchers at Drug Product Services in this special, in-house episode of the podcast "A View On."

EPISODE 4: Cannabinoid-based medicines

Not Your Parent's Weed: A Synthetic Cannabinoid Derivative Reaches Clinical Trials for Autoimmune and Fibrotic Diseases

Dr. Alain Rolland, Chief Operating Officer & Executive Vice President of Emerald Health Pharmaceuticals, talks to Lonza about using novel synthetic drug candidates derived from cannabinoids for unmet medical needs.

Cannabinoids are emerging as a serious treatment option for autoimmune and other immune-related diseases thanks to their modifications as synthetic derivatives. Emerald Health Pharmaceuticals (EHP) has widened the potential application of cannabinoids by designing cannabidiol (CBD) and cannabigerol (CBG) derivatives that have a greater effect on the endocannabinoid system and can even interact with receptors and pathways from other biosystems to treat autoimmune and fibrotic diseases. Advances by EHP and others are contributing to the larger acceptance of those novel molecules by the medical community and regulatory authorities. These are exciting times for cannabinoid researchers at EHP and their investors, given that the company has begun enrollment and dosed its first patients with diffuse cutaneous systemic sclerosis (dcSSc) in its Phase 2a clinical study of EHP-101, EHP's oral formulation of a patented new chemical entity (NCE) derived from CBD, and preparations for the initiation of a Phase 2 study in multiple sclerosis are planned for later this year. In addition, EHP-102, an oral formulation of a patented NCE derived from CBG, is in preclinical development for the treatment of Parkinson's and Huntington's diseases.

Curious to Know More?
Listen to the conversation between Lonza and Emerald Health Pharmaceuticals in this episode of the podcast "A View On."

EPISODE 3: Mesenchymal stem cells for COVID-19 treatment

Off-the-shelf Cell Therapy Remestemcel-L Targeting the Lethal Complication of the COVID-19 Pandemic

Mesoblast CEO Dr. Silviu Itescu speaks to Lonza about the company’s advanced portfolio of anti-inflammatory allogeneic cellular medicines including remestemcel-L, which is currently being evaluated in a U.S. Phase 3 randomized controlled trial for acute respiratory distress syndrome (ARDS), the principal cause of mortality due to COVID-19 infection.

Most COVID-19-related deaths result from ARDS, an overactive immune response that creates overwhelming inflammation in lung tissue. As the world suffers in the grip of this pandemic, some hope comes from Mesoblast. They have dedicated the past 15 years to developing a portfolio of product candidates based on mesenchymal lineage cells to treat severe inflammatory diseases such as graft versus host disease, advanced heart failure, and chronic low back pain. Their strategy for treating inflammatory diseases uses cellular medicines instead of small molecules or monoclonal antibodies, thereby treating an out-of-control immune system on a systemic level by impacting multiple inflammatory pathways at the same time. This positions them well to provide much-needed treatment for those COVID-19 ARDS patients left with few – or no – options. The Phase 3 trial was informed by the positive results from an emergency compassionate use protocol in patients on mechanical ventilation with COVID-19 ARDS at Mt Sinai Hospital in New York where 75% (nine of 12) patients were discharged home compared to a mortality rate of around 80% recorded in New York over the same time period in patients with COVID-19 ARDS who were not treated with remestemcel-L. Interim analyses of the 300-patient trial are planned, and Mesoblast Chief Executive Dr. Silviu Itescu is eagerly awaiting results.

Curious to Know More?
Listen to the conversation between Lonza and Mesoblast Chief Executive Dr. Silviu Itescu in this episode of the podcast, "A View On."

KEY TERMS:

Cellular medicine: The use of cells already found in the human body, frequently modified and enhanced, to treat diseases.

Mesenchymal lineage cells: Cells whose function is to sense tissue inflammation through specific receptors for inflammatory cytokines and then secrete anti-inflammatory factors. They are present in all vascularized tissue and act as regulators that enable normal immune response in all organs. To learn more, visit: www.mesoblast.com/science/mesenchymal-lineage-cells.

Immune cascade: When the body’s complementary immune system produces additional proteins, such as cytokines, to enhance the ability of antibodies to defend against microbes and damaged cells.

Cytokines: These extremely small proteins, important in cell signaling, modulate immune responses. Mesoblast’s mesenchymal lineage cells interact with cytokines to modulate the inflammatory response of the immune system.

Cytokine storm: This is when the body quickly releases too many cytokines into the blood, creating an exaggerated immune system inflammatory response that can be harmful and even deadly.

Multimodal immune activation: When the body activates multiple immune responses to attack a virus or foreign body, potentially leading to dangerous inflammation of tissues in vital organs. The advantage of Mesoblast’s technology is that, unlike small molecules and monoclonal antibodies, their cellular medicines can simultaneously regulate several of these responses.

New Arsenal in the Battle Against Cancer: Pharmaceutical Smart Bombs Promise Less Collateral Damage for Patients

Cybrexa Therapeutics CEO Per Hellsund and CSO Vishwas Paralkar talk to Lonza about how their enterprise is shaping the future of cancer treatment with cell-penetrating peptides.

One of the biggest obstacles to safely eliminating cancerous cells is that most therapies also negatively impact a patient's healthy organs and tissues, known as bystanders. This notorious problem has hindered effective treatment since the beginning of oncology and often has devastating effects on patients’ quality of life. One novel strategy pursued by Cybrexa Therapeutics is the design of treatments that specifically target solid tumors made of cancer cells by taking advantage of one of their universal biomarkers – acidity. The company has developed a platform that leverages the low pH environment inherent to cancer cell metabolism. By using cell-penetrating peptides bearing an anticancer cargo load, their platform brings the treatment directly inside tumors, leaving healthy cells alone and minimizing bystander killings. This smart anti-tumor technology promises to be applicable to a wide swath of patients and reduce side effects of cancer treatment

Curious to Know More?
Listen to the conversation between Lonza and Cybrexa Therapeutics researchers in this episode of the podcast "A View On."

KEY TERMS:

Acidity of cancer cells: Current research shows that cancer cells exhibit a type of cell metabolism known as aerobic glycolysis, a process that generates lactic acid and creates a more acidic environment in and around tumors.

Cell-penetrating peptide: Peptides are strings of amino acids that can be utilized for drug delivery. They are wobbly in structure and ineffective at penetrating cells under normal pH levels but rigidify when reaching acidic environments and can then enter the targeted cell.

Linkers: A chemical bond that allows for a drug to attach to its carrier and be delivered to a specific target. For Cybrexa, this bond connects the peptide to the cytotoxic molecule or DNA inhibitor for efficient targeting of cancer cells and tumors.

Cytotoxic drugs: Cytotoxic drugs in cancer therapy, such as chemotherapy, are not only toxic to cancer cells but do damage to other healthy cells, creating unwanted side effects to treatment. New research is showing how, when combined with cell-penetrating peptides, cytotoxic molecule delivery can be limited to the acidic environments of cancer cells, thereby avoiding off-target toxicity and bystander killings.

DNA repair inhibitors: A relatively recent form of cancer treatment that oncologists often use in conjunction with chemotherapy. Inhibiting the repair mechanisms of cancer cells effectively turns the table on the tumor, the cancerous cells of which have hijacked the healthy DNA of a patient and use the cells natural repairing properties to become resistant to chemotherapy. By employing DNA repair inhibitors targeted specifically to cancer cells, researchers hope to increase the effectiveness of chemotherapy and reduce its side effects.

Dose-limiting toxicity: When the side effects of a drug or other cancer treatment prohibit a dose increase that would otherwise be beneficial to the cancer therapy. By removing this boundary, therapies could be much more efficient in destroying cancerous cells in the body.

From the International Space Station to Desktop Printers, 3D Bioprinting Is Revolutionizing Tissue Model Research

Allevi CEO Ricky Solorzano talks to Lonza about how his company is empowering scientists to print their own tissue models

Scientists have been printing cells for decades, but with the arrival of 3D bioprinters, getting printed tissue models to behave like living tissue has proved elusive. That is why angiogenesis and vascularization are two holy grails of 3D bioprinting. A recent article published by researchers at biotech company Allevi demonstrates breakthrough research in which a skin tissue model printed on one of their desktop models showed both processes simultaneously. The April 2020 publication in ACS Biomaterials, Science & Engineering illustrates just how fast bioprinting is moving, producing results that were unimaginable five years ago, facilitating the study of tissue models in basic science, disease modeling, and drug discovery. But Allevi is not stopping at Earth-bound breakthroughs. The US company has also secured funding for simultaneous bioprinting experiments on the International Space Station.

Curious to Know More?
Listen to the conversation between Lonza and Allevi CEO Ricky Solorzano about both the current state of bioprinting and its future applications in the first episode of the podcast “A View On.”

KEY TERMS:

Desktop 3D bioprinting: 3D bioprinting, a process similar to other additive manufacturing techniques, uses bioinks and biomaterials to create biomedical parts for research like skin tissue and organoids such as corneas. These printers have traditionally been voluminous, complicated, and costly. Allevi’s desktop 3D bioprinters are not only smaller, they are easy to use and significantly less expensive than larger models.

Bio-extrusion: A standard 3D printer at home or in a maker lab makes an object by adding material layer by layer. In bio-extrusion, bioinks are extruded from the nozzles and printed onto a biomaterial matrix.

Bioink: A material composed of living cells and biopolymer gels that, once extruded by the printer, can be organised into tissues, organs, and organoids.

Matrigel™: The trade name for the substrate used for culturing cells, essential in the bioprinting process as it is often the surface onto which the bioink is printed.

Angiogenesis: From ancient Greek, literally the creation (genesis) of vessels (angio). In modern biology, the term refers to the formation of new blood vessels within a tissue. In bioprinting, the presence of angiogenesis means that the printed tissue is behaving and growing in a way that is akin to living tissue and is essential to the success of creating functional printed tissues and organs.

Vascularization: Also related to the creation of blood vessels but, in contrast to angiogenesis, successful vascularization of a printed tissue is when an existing, printed structure of blood vessels is adopted by the tissue to delivering blood throughout the structure.

Innervation: The process by which a tissue is supplied with nerves. In 3D bioprinting, supplying a printed tissue with nerves is the latest frontier of the technology as supplying tissue not only with blood but also nerves could possibly accelerate restoration of muscle function in vivo and create more complex tissue models for research on neurological diseases.

For the above-mentioned article on angiogenesis and vascularization as well as the latest on bioprinting research, you can read more on the Allevi Blog.