Episodit
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Simulating the Journey of Oral Medications: A Leap Towards Personalized Medicine
In this episode, we are joined by Deanna Mudie, a senior principal engineer at Lonza, and John DiBella, president of PBPK & Cheminformatics at Simulations Plus, to discuss new techniques in enhancing the bioavailability of drugs.
When you swallow a pill, have you ever pondered the intricate journey it undertakes to deliver its therapeutic effect? This voyage, crucial for the drug's effectiveness, is at the heart of pharmaceutical R&D's quest to enhance bioavailability - the proportion of the drug that enters circulation and reaches the target area.
By simulating how drugs interact with the body, scientists can optimize therapeutic outcomes by tailoring medications to the needs of individual patients. This approach promises a future where drugs are not only more effective but also safer, with reduced side effects. Listen as we delve into the cutting-edge world of Physiologically Based Pharmacokinetic (PBPK) modeling. These computer models integrate factors like gastrointestinal physiology and population characteristics, shedding light on how drugs behave in various body systems without the need for extensive patient testing.
Curious to Know More?
Join us in this conversation hosted by Martina Hestericová with Lonza's Deanna Mudie and Simulations Plus's John DiBella as they unveil the potential of PBPK modeling to revolutionize drug development and personalized medicine.
KEY TERMS IN CONTEXT:
In the context of pharmaceuticals, drug bioavailability refers to the proportion of a drug that enters the circulation when introduced into the body and is thereby able to have an active effect. It's a critical factor in determining the drug's effectiveness, as it measures how much of a drug in a dosage form (like a tablet or injection) becomes available at the target site of action.
PBPK modeling is a sophisticated computational modeling technique used to predict the absorption, distribution, metabolism, and excretion (ADME) of drugs within animals and humans. This approach aids in understanding a drug's bioavailability and supports the design of more effective and safer drug therapies.
Gastrointestinal Physiology refers to the study of the functions and processes of the digestive system or gastrointestinal (GI) tract. In the context of PBPK modeling, understanding gastrointestinal physiology is crucial for predicting how a drug is absorbed into the body, especially for orally administered medications. It includes factors like stomach acid levels, GI transit time, and the surface area available for absorption.
"In silico" refers to the use of computer simulations or digital analyses to conduct experiments or procedures virtually rather than in a laboratory or real-world setting. In silico tools in drug development include software and algorithms used for modeling and simulation, such as PBPK models, which allow researchers to predict how drugs interact with animals and humans, aiding in drug design, testing, and the customization of therapies for personalized medicine.
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Capsules for Targeted Therapy: A Game-Changer in Modern Medicine
In this episode we are joined by Vincent Jannin, Lonza's R&D Director, to explore Enprotect, the Award-Nominated Capsule Technology.
Imagine starting your day with a simple capsule that goes beyond simply dissolving in your stomach to reach the place in your body where it is needed most before releasing its medicine. That’s just what Lonza’s Enprotect enteric capsules do. They are designed to release medication directly into the small intestine, which represents a significant leap in pharmaceutical delivery. They improve patient compliance without increasing production costs and offer targeted delivery for specific therapies such as live biotherapeutic products. This targeted approach is crucial for treatments that require local delivery, for example for Crohn's disease, exocrine pancreatic insufficiency, or Clostridium difficile infection.
In this episode we hear from Vincent Jannin about how advances in polymer science have ushered in this new era of capsules capable of targeted drug delivery. This marvel of modern medicine combines the fields of chemistry, nanoscience, biology, and physics. The creation of a bilayer capsule—comprised of a structural layer for shape and a functional layer for targeted release—both required the development of new technologies and could itself serve as an enabling technology for future therapies.
Vincent Jannin and his team have published several peer-reviewed studies in open access scientific journals, which were mentioned in the podcast:
In Vivo Evaluation of a Gastro-Resistant Enprotect Capsule under Postprandial Conditions (https://www.mdpi.com/1999-4923/15/11/2576) In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule (https://www.mdpi.com/1999-4923/14/10/1999) In vitro evaluation of the gastrointestinal delivery of acid-sensitive pancrelipase in a next generation enteric capsule using an exocrine pancreatic insufficiency disease model (https://www.sciencedirect.com/science/article/pii/S0378517322009966)Curious to Know More?
Join us this episode as we explore the journey from a simple capsule to a sophisticated drug delivery system and how this advancement reflects a remarkable fusion of science and innovation. Discover how the Enprotect technology not only offers hope for more effective treatments but also exemplifies the relentless pursuit of medical advancement for the benefit of patients everywhere.
KEY TERMS IN CONTEXT:
An enteric capsule is a type of capsule specifically designed to bypass the acidic environment of the stomach and release its contents into the small intestine. The term 'enteric' relates to the small intestine. These capsules are formulated to remain intact in the stomach and dissolve only when they reach the more neutral pH levels of the intestine, ensuring targeted drug delivery.
Enteric polymers are materials used in the construction of enteric capsules. They are chosen for their ability to withstand acidic conditions (like those in the stomach) and dissolve at higher pH levels like those found in the small intestine. HPMC Acetate Succinate is an example of an enteric polymer used for the outer layer of the capsule to ensure the treatment’s proper dissolution and release in the intestine.
Live Biotherapeutics (LBPs) refer to live microorganisms used for therapeutic purposes. They are designed to interact with the human microbiome, particularly in the small intestine, and are sensitive to stomach environments. The protection LBPs need before their release in the desired intestinal location is facilitated by specialized capsules.
Fecal Material Transfer refers to a medical treatment involving the transfer of fecal matter from a healthy donor to a patient, often used for conditions like Clostridium difficile infections. The podcast highlighted the potential use of enteric capsules for the delivery of such treatments directly to the small intestine, thereby offering an alternative to more invasive procedures.
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Puuttuva jakso?
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Embark on a microscopic journey into particle identification — the unsung hero of pharmaceutical safety — and uncover how this vital process shields us from unseen threats in every single medication we take.
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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.
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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 its 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 IN CONTEXT:
A Chimeric antigen receptor (CAR) is a synthetic receptor engineered to be expressed on the surface of immune cells, particularly T cells, allowing them to recognize and bind to specific molecules or antigens present on cancer cells, triggering their destruction. CARs play a crucial role in CAR-T cell therapy by redirecting the immune cells to target and eliminate cancer cells with precision.
CAR-T cell therapy is a revolutionary form of immunotherapy that involves engineering T cells to express CARs on their surface. These modified CAR-T cells are then infused into the patient, where they can recognize and target cancer cells, leading to potent and often long-lasting success with remission.
Personalized medicine tailors medical treatments to individual patients based on their unique characteristics. In the context of CAR-T cell therapy, it involves genetically modifying a patient's own immune cells for customized and targeted cancer treatment.
Autologous therapy is a CAR-T cell therapy approach that uses the patient's own T cells for manufacturing, whereas allogeneic therapy utilizes donor T cells as a cell source, offering potential advantages in terms of scalability and accessibility.
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Lonza experts Selene Araya and Charles Johnson discuss the manufacturing process, trends, and future of highly potent compounds (HPAPIs). They highlight Lonza's facilities and expertise in producing HPAPIs across various technologies and scales, ensuring advanced containment and addressing bioavailability challenges.
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Ian Thomson from Ypsomed and Roman Mathias from Lonza discuss the market trends in injectable delivery devices, their manufacturing process, and their future in sustainable pharma. Injectable devices offer various benefits, including improved convenience, accuracy, and safety, allowing for precise dosing while reducing the need for hospital visits.
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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.
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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 stimulate the immune system’s first line of defense – 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 inhalers, 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 Delivery.
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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.
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Developing Cell Culture Media For Growing Cells
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 cultivated 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 recipe 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 production or make the tastiest animal-free cultivated cordon bleu on the planet.
Curious to Know More?
Listen to this episode of A View On to learn more about what it takes to grow cells in a lab. As a bonus for our listeners, at the end of the discussion, Alexis Bossie shares insights into the possibilities and obstacles of growing meat in the lab.
KEY TERMS IN CONTEXT:
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 functioning. 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 quantities 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.
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 outcome.
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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.
Interested to learn more? Visit our dedicated podcast site on www.lonza.com/a-view-on and don't forget to subscribe.
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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 IN CONTEXT:
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.
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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.
An evolving toolbox of technology and advanced scientific knowledge is fueling the growth of a wide range of next-generation drugs in today’s pipelines. These novel but complex products, while offering the ability to treat previously unmet medical needs across the globe, also present many challenges. This is often due to their unique profiles that require bespoke development and manufacturing processes as opposed to using well-known platform approaches, adding even more risk to a space fraught with uncertainty. This increasingly competitive market leaves little room for error or delay. Therefore, selecting and optimizing the right lead candidate becomes critical, as this allows you to de-risk your drug development process and maximize your chances of success.
The largest cause of failure during drug development is most often related to safety and efficacy, so it is important to have processes in place that can identify potential issues as early as possible. Simple, cost-effective in silico and in vitro assessments can help look at potential developability challenges in the earliest stages and allow for modifications to the drug candidate and its process development to mitigate potential efficacy, safety or manufacturability risks.
Many of the drugs currently in early development around the world are initially developed by small biotechs, companies that often require the support of service providers to assist and to accelerate the de-risking of their candidates This is where Lonza’s Early Development experts step in. Today’s guest is Raymond Donninger, Senir Director of Commercial Development for Lonza’s Early Development Services in Cambridge.
To start the de-risking process, the team can predict development issues very early, based on the candidate’s sequence and structure. This knowledge allows for modifications to the drug candidate and its process development to mitigate risk early and increase the likelihood of a successful first-in-human study. The experts then also apply in vitro tools to look at developability challenges and to mitigate potential efficacy, safety or manufacturability risks.
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 Director of Commercial Development for Lonza’s Early Development Services.
KEY TERMS in Context:
In silico immunogenicity and human cell in vitro assays are two essential ways to de-risk a molecule’s development pathway . In silico tests run computer models to predict a molecule’s interaction with the human immune system; in vitro testing assesses the molecule’s interaction with human immune cells.
The attrition of a drug candidate 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.
Attrition happens when a molecule has therapeutic potential but safety, target engagement or developability (for example complex, uneconomic manufacturing processes) issues prevent the product from reaching the market. The de-risking process aims to reduce attrition to improve the chances for viable and safe therapies to make it to market.
According to Donninger, a T-cell epitope is a sequence within the protein that has the potential to allow the immune system to recognize it as being foreign and then mount an unwanted and potentially dangerous immune response. To learn more about de-risking and immunogenicity, listen to this season’s Episode Five.
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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 IN CONTEXT:
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.
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Antibody-drug Conjugates: Next-Generation of Targeted Cancer Treatments
Iwan Bertholjotti and Laurence 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 IN CONTEXT:
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.
Scaling up production for bioconjugates involves moving from manufacturing small batches for clinical trials to large batches up to five kilograms for commercial production. This major challenge for companies is essential for the successful commercialization of ADCs.
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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 IN CONTEXT:
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.
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In this reposted episode from December 2020, we're exploring how a better understanding of exosomes is leading to new treatments and diagnostic technologies with Uwe Gottschalk.
According to Uwe, 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?
Listen to our special, in-house episode of the podcast "A View On" and tune in next time as we are exploring the manufacturing challenges of exosome-based therapies with Codiak Biosciences.
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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 IN CONTEXT:
Anti-drug antibody (ADA) response happens when the patient’s immune system generates antibodies to remove and clear the drug from the body. This can impact the effectiveness of the drug molecule as well as be dangerous for the patient.
Immunogenicity testing is the process by which one can test for the body’s immune response to a drug. With in-silico testing, the screening can be done quickly for a large swath of different immune system typologies before moving on to animal models or, preferably, human cell assays.
Immunosafety and immunotoxicity refer to how potentially safe or toxic the immune system’s reaction to a molecule may be. They deserve the utmost consideration when developing a leading drug candidate.
De-risking is an EDS drug development strategy to ensure clients select the right drug candidate at the approval phase. De-risking avoids costly clinical trial failure through extensive immunotoxicity testing early in the process.
In-silico testing uses computer models to test a molecule’s reaction within an organism, such as a human immune system. The advantage is that they are quick and can test in hundreds and thousands of models. Since they are limited in their nature, they are only a first step. Once a drug candidate is selected as low risk using in-silico testing, further testing is needed using animal models or human cells assays.
Human cell assays, in the context of drug development de-risking, are in-vitro tests that use actual human immune cells to test immune system responses to drug candidates. Although they are more costly and time-consuming than in-silico testing, the precision they offer is essential to establish the appropriate data for selecting lead drug candidates.
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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 on 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 diseases.
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 IN CONTEXT:
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.
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