Discoveries in technology, medicine, and nutrition are emerging with accelerating speed and improving our health and quality of life. Brought to you by Lonza, “A View On” podcast is a series of short conversations with industry leaders. Join us to discuss new trends that are impacting scientific research, drug discovery and business.

The series of monthly conversations with pharma, biotech and nutrition leaders from across industry and academia covers a wide range of topics from 3D bioprinting to therapeutic cannabinoids. In under ten minutes, each podcast takes the audience on a rapid but deep dive into an exciting development that promises to profoundly change or even revolutionize healthcare.


EPISODE 4: MICROBIOME

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:

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.

Season 2

  • 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.

    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.

    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.

Season 1

  • 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.

  • EPISODE 8: “Exosomes”

    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.