January 7, 2022 PAO-12-21-RT-01
Austin Mogen, Ph.D., Senior Field Application Scientist, Corning Life Sciences
A: One of the major limitations of drug development efforts has been the lack of laboratory models that capture the complex biology of cells in our bodies. With the advent of technologies that allow the growth of cells in three dimensions, such as Corning® Matrigel® matrix, Corning spheroid microplates, and Corning Elplasia® plates, it is now possible to culture patient-derived mini-organs, or organoids. The ability to grow mini-organs in a laboratory allows researchers to build robust disease models that are tailored to the individual. Toxicity studies and drug screening can then be completed to confirm that the treatments are personalized and appropriate for the unique patient. Right now, two emerging areas of innovation include adding complexity to the organoid model and increasing throughput. A solution to both of these challenges is the Corning Matribot® Bioprinter, which allows for bioprinting of more complex disease models and automated dispensing of organoid droplets.
Brian Graves, Global Business Manager, Grace Materials Technologies
A: At the heart of personalized and precision medicine is data. The ability to diagnose a condition and prescribe a therapy has been at the core of medicine dating back to Imhotep, who lived in the 27th century BCE (nearly 5000 years ago) and prescribed courses of treatment for a range of maladies. Today, we can map the human genome, as well as the genomes of various cancers; we are also developing an understanding of epigenetics and how that translates into conditions such as disease and aging.
Our understanding of the biological processes unfolding within our bodies continues to grow, and our ability to make use of this immense set of data through AI and advanced data analytics will be a driving force behind the development of personalized therapies. It will lead to accelerated advancement of complex and novel therapies, such as gene editing and RNA medicines, and the ability to treat conditions, such as cystic fibrosis, muscular dystrophy, forms of blindness and sickle cell anemia, at the genetic level.
The use of AI and data analytics to determine whether previously developed therapies can be used for other conditions or whether more traditional types of therapies, such as a small molecule drug, can be applied to what have been thought to be “large molecule” problems has the potential for great impact. These “innovations” could touch far more lives in the near term than advanced treatments that may be available to a relatively small portion of the worldwide population.
A: Traditionally, the goal for drug developers has been to create therapies that would be the drug of choice for all, thus capturing a large market. However, we now realize a one-size-fits-all approach is not always realistic, especially with cancer indications where, even within tumors, the individual cancer cells may harbor unique combinations of genomic and epigenomic events. Identifying “driver” mutations and targeting the proteins derived from these genomic events has been the route followed most often, and we now have therapeutics that target many mutated kinases and translocation fusion proteins.
There are many therapeutic approaches emerging that differ in their approach. Examples include immunotherapies; targeted degraders, such as PROTACs; and even synthetic lethal drugs. Key innovations for personalized/precision medicine may come from advances in biomarker discovery and monitoring technologies. This includes new experimental modalities in the detection of markers in serum samples but may also involve completely novel screening approaches that enable us to determine when to use a targeted drug, how patients are responding, when to adjust the dose, and when to switch to an alternative therapeutic approach. I feel that personalized medicine will truly be the norm when we have the knowledge base, technology, and willingness for rapid and periodic monitoring of biomarkers for each patient.
Personalized medicine allows patients to receive treatments tailored to their genome. A prerequisite of personalized medicine is therefore being able to sequence a patient’s genome rapidly and affordably, which is becoming more of a reality every passing day. By examining an individual’s genome, we can look for patterns that might indicate risk of disease and identify tailored treatment solutions. mRNA therapeutics are one of the key tools for providing tailored treatment solutions for patients. Developing mRNA–LNP platforms where the information encoded in the platform can be rapidly exchanged more easily will be critical for personalized medicine. Once the mRNA therapeutic has been adapted and fine-tuned for a patient or group of patients, being able to manufacture these at the appropriate scale will be essential. Evonik, for example, is fully integrated across the value chain and can provide clinical to commercial drug product manufacturing capability at the smaller scales compatible with personalized medicine.
A: Right now, the frontrunner for cell and gene therapy treatments is CAR-T, which works well for hematological cancers, but to date has had limited success with solid tumors. CAR-NK offers potential for an allogeneic product, as solid tumors are a frontier yet to be reached.
Another consideration would be advancing CAR-NK therapies, which take natural killer cells that are allogenic from patients or donors. This means that one CAR-NK therapy can be used for many patients off the shelf, rather than the need for autologous treatment, such as CAR-T therapies that require a custom CAR-T product produced for each patient. With an allogeneic therapy, you get the benefits of scale and consistency, as well as less challenging regulatory compliance with increased safety for the patients. There's a lot of opportunity in that space.
A: At SOPHiA GENETICS, we continue to rapidly evolve the landscape of precision medicine, and our platform users have already experienced tremendous growth in what they can accomplish through more comprehensive next-generation sequencing aided by elite machine learning. A determining factor is our ability to expand the scope of what clinical researchers can discover in a single assay while also maintaining and advancing the levels of accuracy and meaningful insights for those tests. But this is only one piece of the puzzle when it comes to precision medicine. Combining various types of health data from a patient’s genomic data, medical imaging, clinical trials, or even personal wearable devices with real-time health monitoring will bring a truly multimodal approach to the landscape that will allow physicians to get a comprehensive 360° view of an individual.
A: There have been tremendous leaps in recent years related to precision medicines. Advances in our understanding of biomarkers and cell therapy applications are helping to radically redefine what is possible for patients; however, for all of the advancements, many of these technologies are only useful for a small subset of patients. As we look to the next wave of precision medicine, researchers must explore mechanisms for expanding the impact of these technologies to larger patient populations. It will take bold new ideas to advance the science, and that is a key reason why we at Double Rainbow are focused on developing platform technologies that can help deliver a new era of medicine.
When you explore the history of medicine over the past 50 years, most major advancements have resulted from platform technologies that were previously thought impossible. Our team is working to provide the next step in that innovation journey by harnessing the full potential of synthetic biology to create precision glycosylated therapeutics with enhanced targeting, safety, and bioavailability. By combining the progress of precision medicine to date with previously underexplored sugar chemistry, we are taking a well-established natural process in glycosylation and leveraging it with unprecedented precision to affect human health.
Our goal is to leverage the vast presence of glycans on cells and proteins to enable a new field of targeted drug development and discovery. As our team continues to push the limits of our technologies, we believe that the advancement of our PRISM platform could create new targets for immuno-oncology, improve drug delivery across the blood–brain barrier, and even manipulate the microbiome for drug absorption. Work is underway to further validate glycosylation as a novel therapeutic modality, and our team remains focused on our goal of delivering safer, more effective medicines to the patients we serve.
A: Autologous cell therapy, which involves manipulating cells outside a person’s body and then readministering them to the patient, is one of the most exciting innovations in personalized/precision medicine. The process involves augmenting the cells taken out with a stronger missing gene and then reinforcing the patient’s immune system with this improved cell. Autologous therapies can help combat immunological reactions or bio-incompatibilities, such as when a substance produces a toxic response in the body. They can also serve as skin substitutes, treating burns, wounds, and chronic inflammation. This method relies on the intrinsic ability of blood stem cells to reproduce and create this new and improved form of a cell. In the last year and a half, we have seen a lot of attention around mRNA vaccine techniques, which have become mainstream for producing antibodies, but autologous cell therapies could be the next medical innovation we bring to the masses.
A: Disease characterization and therapeutics development are obviously crucial components of personalized medicine, but the real gatekeeper will be scalable manufacturing — it already is. The few autologous cell therapies on the market today are struggling to meet patient demand. These therapies are made from a patient’s own cells using techniques not well standardized to develop bespoke living drugs. As a result, they come at a high cost for patients in desperate need who have typically stopped responding to all other treatments.
The pharmaceutical industry has been built to scale identical therapeutics to treat many people with similar disease profiles, but potential curative treatments like cell therapies are customized for both the subtype of disease and the traits of the individual patients. In other words, the trend of mass customization has reached healthcare. To meet the challenges of this new healthcare paradigm at large scale and modest per-patient cost, we need true end-to-end automation and software-defined manufacturing.
There are several pain points where automation is able to accelerate manufacturing, improving reproducibility and decreasing reliance on limited human technical expertise. These include cell activation, in-process sampling, media exchanges, quality check, cell processing, and more. Our approach at Cellares is to create true end-to-end process automation within a customizable enclosed system that can manufacture up to 10 different therapeutic products simultaneously. This agile and automated approach will ultimately make truly personalized therapies accessible to everyone who needs them.
A: Advanced molecular diagnostics have had a huge impact on precision medicine in areas like prenatal care, transplant medicine, and oncology. But the future of precision medicine lies in other areas of medicine as well, like infectious diseases.
In the past, cancer has been a major focus of the precision medicine initiative. People get very excited about advancements in treating cancer, because we’ve all been touched by it; everybody has someone they know who’s struggling with cancer. But now is the time where we need to take these advanced diagnostics technologies and move them into other areas of medicine — for example, mental health, infectious disease, and other conditions where genomics can have a dramatic impact on the care and outcomes of patients.
Right now, there’s a lot of conversation about making sure that we’re leveraging technology so that people get the best therapies based on the best information possible and in the most targeted way. A “one-size-fits-all” approach to medicine won’t give us the best results anymore, whether it’s for cancer or infections. We have fewer new drugs in infectious disease, drugs that work less well over time, and a threat is increasing relative to our ability to treat patients effectively. The diagnostics we use are also decades old.
The start of precision medicine for infectious diseases has been spurred with molecular diagnostics like the Karius test — the first liquid biopsy for infectious diseases that can detect >1000 pathogens from a single blood sample for infections located throughout the body.
A: We’ve seen tremendous biomedical progress in recent years that has introduced us to this concept of precision medicine that would replace the “one-size-fits-all” treatment approach for cancer and many other diseases. But the future of these advanced personalized medicines relies on technologies that provide deeper access to in vivo biology to create durable, curative impacts on health. By gaining this type of cellular and molecular access, I believe that we can shift paradigms in cell and gene therapy, cancer immunology, and infectious disease toward more patient-specific, long-lasting treatments.
The technologies we are advancing at IsoPlexis give insight into single-cell biology and functional proteomics. In other words, we are probing the immune system to reveal unique immune biomarkers in small subsets of “superhero cells.” These superhero cells are essentially turbocharged immune cells that orchestrate how an individual responds to treatment. Now, for the first time, we can identify and predict how these superhero cells communicate and respond much earlier in the clinical process, by way of a variety of molecules like proteins and cytokines. In this manner, we can “tune” immunotherapies and targeted therapies at the cellular behavior level so that they are more highly precise and personalized.
Not only that, but I also think it’s incredibly important to be able to leverage the same cell to produce protein maps and genetic maps. Our technologies are finally connecting one to the other to reveal direct pathways that would be missed if you were averaging across a large group of cells.
A: Key innovations and technologies that have the potential to significantly impact personalized/precision medicine address the following:
The number of personalized and custom-engineered therapies in R&D and preclinical stages has grown exponentially. However, even for the most advanced initiatives, a major bottleneck is still the transition to clinical-scale production. Developing fully automated systems able to sustain the scale-up and scale-out needs and to yield a consistent product for every patient will represent a major step in advancing the field.
Having a more thorough understanding of underlying disease initiation and progression will help to identify critical biomarkers that are relevant to therapy. In turn, this will have a tremendous impact on: (a) tailoring therapies to specifically target critical aspects of the disease and (b) selecting and stratifying patients more accurately in clinical studies, thereby increasing the effectiveness and success of a therapeutic intervention.
This is especially relevant for cell therapy products, which are “living drugs” that evolve in the course of treatment. With advancements in technologies that expand analytical capacity and accommodate small sample sizes, we will gain better insights into critical aspects associated with function, fitness, toxicity, and longevity of therapeutic products. This information, in turn, will help to inform on therapy strategy and will guide appropriate clinical trial designs for each indication and patient population.
A: We have to acknowledge analytical innovations’ ongoing contributions in target and lead discovery. Next-generation sequencing (NGS) and RNA-Seq technologies have enabled a much deeper understanding of disease biology at the genomic and transcriptomic levels. Innovations in mass spectrometry (MS) (tandem-MS and high-resolution MS) have delivered insights into the expression (proteomics) and activity (metabolomics) of proteins in relation to disease.
A deeper understanding of biology has delivered innovative new drugs and therapeutic approaches that, to us, signal precision medicine’s rising presence in the clinic. Multispecific drugs are a great example. The drug modalities within this category exploit biological processes — “normal” and pathogenic — to deliver impressive levels of therapeutic target specificity. We applaud antibody–drug conjugates (ADCs) as one of the most mature multispecific drug innovations. We are excited to see and support the further induced proximity innovations emerging — for example, chimeras that harness cells’ endogenous protein degradation machinery to eliminate known or suspected disease-related proteins (e.g., PROTACs, LYTACS).
We believe that the impact of innovative drug delivery technologies on the future of precision medicine cannot be understated. Highly engineered lipid nanoparticle delivery systems, designed for the pH-triggered release of nucleic acid–based vaccines in the cytosol, have proven very effective in the fight against SARS-CoV-2. These and other delivery innovations, such as synthetic exosomes, allow us to imagine a future in which medicines can access protein or gene targets within the cell, with payloads ranging from small molecules to mRNA. We are extremely encouraged about precision medicine’s near-term prospects. We feel privileged to support innovators who are bringing them to life.
A: One of the primary challenges for effective personalized/precision medicine is the stabilization and delivery of RNA. So, we see our silicon-stabilized hybrid lipid nanoparticles (sshLNP) technology as the key innovation that will make precision medicines a reality.
A: Historically, traditional therapeutics aim at developing the same drug (e.g., aspirin) for everybody. Personalized medicine, on the other hand, pursues development of targeted drugs for a specific group of patients. This new therapeutic approach uses companion diagnostics to see which patient would benefit from the treatment. Companion diagnostics simply test patients for a predictive biomarker, classifying them into responders and non-responders. An example of this approach is the development of a therapeutic antibody that is specific for a molecular target within the patient.
With widespread growth in predictive technologies, personalized therapeutics has advanced into manufacturing individualized medicine so that each patient receives their own unique treatment. This approach is contingent upon having access to high-quality data on the genome of a large group of patients. This would enable us to couple a patient’s biological sample to comprehensive clinical data, leading to the most effective individualized therapy. Given that the human genome contains about 3 billion DNA base pairs and about 25,000 genes, advanced computational methods in genome sequence analysis serve as the foundation for producing individualized therapeutics.
A: Across the globe, we’re witnessing the rapid transformation of healthcare and medicine driven in part by biopharmaceutical product advances and aggressive biotechnology research. One of the best examples of this is genomics, a term I hear often from our life sciences suppliers and customers. Genomic medicine involves scientists studying genes, helping them predict, diagnose, and treat diseases with greater precision and personalization. When it comes to treatment, genomics is driving another vital element of precision medicine — pharmacogenomics, which determines how a person’s unique genetic makeup influences their response to medications.
It’s no secret that a drug in the same form and dosage can affect people differently. That’s because our genes influence the enzymes that metabolize drugs and differ from person to person. Pharmacogenomics means we can test for these gene variations and potentially compensate with alternative medications. What’s making this level of personalized medicine possible? In a word: data. Today, more than 250 drugs labeled with pharmacogenomic information can be prescribed on the basis of a person’s genetics. As this number grows and DNA sequencing becomes more standard, we will likely see more medicines developed and prescribed based on our genes — helping minimize side effects and improving treatments. With genome data, predicting disease and identifying a specific treatment based on an individual’s genetic material is now real.
Univar Solutions supports this fast-evolving industry’s supply chain with compounds, chemicals, and ingredients used in developing and producing finished forms of personalized medicine treatments. Our product line includes buffers, stabilizers, and substances used in protein purification and DNA sequencing. As the discipline advances, so do we, bringing on new suppliers and adding to our offering. With an entire team of professionals dedicated to life sciences, we are keeping a close eye on the unique supply chain needs of this segment and helping deliver the solutions to meet those needs.
A: Advancements in next-generation cell and gene therapies (C>) are bringing us one step closer to the promise of personalized medicine, leading to rapid growth in the C> market. However, this promise is still hindered by the challenges associated with developing them. Due to the complexity of C> therapies, they require a flexible discovery and manufacturing process, and manufacturing must be considered early in process development. No single organization has the complete solution to bringing these transformative therapies to market on their own.
Biopharma companies crave partners who understand the significance of manufacturing in the overall timeline and the potential challenges and also offer the expertise to provide counsel throughout the development process. CROs offer a multidisciplinary bench of expertise and access to innovative technologies to serve as a trusted partner throughout the development journey, creating a streamlined approach for coordination, operationalization, and efficiency.
Further streamlining development activities requires innovative technologies, such as advanced analytics, which are likely to occupy at least two spaces within cell therapy. The first is for profiling patient starting material to assess whether a patient’s cells are sufficient for manufacturing. Analytics can also help identify cell therapy product critical quality attributes (CQAs), which are predictive of clinical efficacy. The second area is intelligent therapeutic target identification and design. As therapeutic candidates make their way into clinical development, these analytical technologies can help predict adverse events. A more complete understanding of the pathways being targeted will enable us to design better, more personalized therapies.
A: The key innovations and technology that we frankly should be expecting and supporting around precision medicine are those that reduce the administrative burden for healthcare systems and staff who provide care delivery and clinical trials as a care option. Personalized medicine requires the data and technology that allow those data to be rapidly synthesized to pinpoint interventional treatment(s) or clinical trial(s) that would best meet a patient’s need. Current infrastructure and technology are not sufficient to address the ever-evolving genomic/molecular data in a sustainable, structured way. Significant manual effort continues around the globe in the healthcare arena, even while genome sequencing is evolving the standard of care, and new novel therapeutics continue to move through discovery to commercialization. The use of electronic health records and associated systems not originally designed for our current expectations has not kept pace with the way data must be structured and used for precision medicine. This exacerbates the manual workload for a highly educated and skilled workforce and takes the time away from patients, and the costs of the manual efforts reduce the margins of the healthcare institutions. Using technology for data and imaging to bring forth those patients who would benefit from personalized medicine, either approved or in trials, will have significant impact on patient lives and will evolve precision medicine faster along the continuum to reality.
A: Several years into the future, we will look back to 2020 and 2021 as the years that the COVID-19 pandemic accelerated the creation of confederated data solutions and brought greater velocity to data use and where decisions were made with greater speed and confidence as a consequence of the combination of real-world evidence (RWE) and randomized control trials — all of which are key to making personalized medicine a reality.
RWE is critical here. The preliminary guidance published by the U.S. FDA on September 30, 2021 was a watershed moment that has brought real-world data–driven evidence generation to the forefront for both registrational and post-approval uses.
Inherent in the words personalized and precision is the ability to (a) access data, (b) contextualize data, (c) bring insights from those data that are meaningful and actionable, and (d) process the data, apply those insights, and take beneficial actions in a timely and relevant way.
RWE supports progress in all of these areas. It accelerates evidence generation with lower costs and time commitments; increases the reliability of data sources and methods; and brings evidence and research to the narrowest and most immediate point of treatment or trial decision.
We also have to look at AI, machine learning, and deep learning. In the FDA’s preliminary guidance, there was a subtle but significant reference to AI. This was auspicious and intentional in being located within the RWE guidance. We are entering the phase where AI will be integrated across the continuum of evidence-generation approaches and clinical decisions. We’re starting to see the broader use of AI for advancing biomedical innovations and as a complementary technology in clinical care — becoming a catalyst for greater value in both.
A: Across therapeutic areas, we’re learning more and more about how and why different patients may have different responses to a given therapy. With that, we know that genetics can play a significant role. As technological innovations allow for deeper exploration into individual phenotypes and genotypes, potentially drawing connections between specific genetic markers and therapeutic response through clinical investigation, the impact could be transformative.
The more we understand about an individual patient’s genetics, and as we have an increasingly enhanced ability to evaluate clinical response based on genetic factors, physicians will be able to better anticipate which of their patients might best respond to a particular therapy — and potentially tailor treatment plans for the benefit of each patient.
Looking even further ahead, the advent and commercial launch of advanced home monitoring devices will offer physicians an unprecedented view into patients’ real-world response to therapies in near real time. The more precise we can get with such tools and insights, the better we can develop and calibrate truly personalized treatment plans for patients that depend on combined critical factors — including genetics, disease activity, and real-time response.
A: Cancer treatment has evolved significantly in recent years, creating new opportunities for people with devastating cancers to find the therapies they need. However, existing drugs target only the most common cancer-triggering mutations, and most mutations are infrequent and remain understudied and unaddressed, even for well-known oncogenes. Fortunately, evolving technological approaches, like functional genomics, are enabling a new future for people who are living with cancer caused by rare mutations and currently have limited treatment options.
At Fore Bio, we aim to develop the targeted therapies desperately needed by patient populations with unaddressed tumor mutations by leveraging our fast-acting, innovative, and powerful genomics capabilities. Our proprietary functional genomics platform, known as Foresight, elucidates disease biology to develop hyper-targeted therapies to patients with rare or unaddressed mutations by identifying candidates that have potential to address patient populations that might otherwise never have found a treatment option. We are building upon decades of expertise in precision oncology to continually refine our scientific and clinical approach to identify and advance potentially impactful therapies by uncovering a detailed understanding of mutation-driven cancers.
A: The growing wealth of knowledge in the drug discovery industry has significantly expanded the potential for specific, targeted cancer treatments. With the deeper understanding of cancer pathways, new drug modalities, and further implementation of patient selection biomarkers that can identify genetic and signaling dependencies, the toolbox for developing targeted cancer therapies has never been so broad. I am hopeful that these technological advancements, which continue to evolve in real time, will allow researchers and physicians to reach what we have been striving for: a tailored, personalized approach to cancer treatment.
These advancements have also allowed scientists and physicians to develop combinations as cancer therapies. My team at Ikena Oncology is developing agents to be used as monotherapies that directly target the underlying mechanisms driving cancer survival and growth, which are also being developed to work in combination with one another or with other existing treatments. We leverage both novel and existing biomarkers in our clinical trials to identify patient subpopulations who we believe have the best chance to benefit from our therapies. Our strategy is a culmination of — and an addition to — the significant progress that has been made in identifying druggable pathways and targets for specific cancer patient populations. Hopefully, it is also a step in the right direction toward personalizing treatment for every person living with cancer. We look forward to exploring the application of these monotherapies and combinations in multiple indications and to working with others who share our mission of making patient-tailored cancer treatments a reality.
A: Once a patient is diagnosed with cancer, the first question usually asked is, “What are my options?” Perhaps a better question to ask is, “What kind of cancer do I have?” In determining therapies that offer the best chance of success, genomic testing may hold the answer. Genomic testing, which identifies mutations in cancer cells, can help provide a more precise understanding of the underlying drivers of the cancer and hence provide insights into the optimal treatment strategy.
Increasing the reach of next-generation sequencing more broadly to community hospitals will allow doctors to make informed decisions that can improve treatment outcomes and the quality of life for patients.
Cancer is fundamentally driven by mutations in DNA. However, these types of mutations are not always the same, even within similar cancer types. This poses a significant problem for new precision approaches targeting specific pathways or molecules only present within certain subsets of cancers.
Next-generation sequencing can identify these mutations and allow doctors to develop tailored treatment strategies that have demonstrated success in cancers that harbor the same or similar mutations. By using a biomarker-informed approach, we can get away from treatment strategies based on the location of the cancer and move toward a tumor-agnostic approach driven by the underlying biology of the disease.
If community hospitals everywhere could follow in the footsteps of academic hospitals and use genomic testing for all cancers, patient outcomes, including both the quality and duration of life, may be vastly improved.
A: While cell therapies offer new opportunities for personalized medicine that we haven’t seen before, autologous-based treatments are expensive to produce and harder for patients to afford. They involve complex processes with short hold times and geographical limitations. These factors create economic issues for developers, medical providers, and, of course, the patients in need, limiting the impact these personalized treatments can have today.
Research shows that a similar type of cell therapy–based personalized medicine — allogeneic treatments — holds the potential for quicker, more efficacious, and more accessible therapies that meet a patient’s individual needs.
Allogeneic therapies offer an economically feasible approach to cell therapy–based personalized medicine. These treatments are simpler to produce, because they do not rely on the logistical challenges of getting cells from the patient to the processing facilities. Furthermore, they offer a standardized and cost-effective approach, which makes creating larger batches more feasible and reduces the risk of contamination. These factors make this treatment type easier to implement than its autologous alternative, creating an opportunity to offer cell therapies for personalized care on a larger, global scale.
With enhancements to our global facilities and capabilities, AGC Biologics is prepared to meet the increasing demand for both autologous and allogeneic therapies and to help find the best ways to produce affordable cell therapy treatments. Further, with recent investments in a new cell and gene therapy facility in Longmont, Colorado, we have untapped resources to bring these more personalized and economical life-changing treatments to market.
A: As evidenced by the number of new gene-modified cell therapies approved in recent years, personalized/precision medicine has arrived. That said, the complexity and cost to manufacture these medicines may make them difficult to expand their use to a larger patient population. It will take breakthroughs in manufacturing and testing to reduce facility/labor/material costs and standardization of safety and release testing to increase availability of these medicines. One example is the standardization of a manufacturing platform to make viral vectors to increase yield and drive down the cost of materials. Also, a switch to allogeneic cell lines will reduce the complexity and cost of gene-modified cell therapies and increase patient access. Finally, improvements in delivery of the medicine to the patient will increase efficacy and reduce dosing requirements, driving down costs and increasing patient access.
I expect you will see great progress in the use of viral vectors for rare disease. Production processes will improve, increasing yield and lowering cost, and innovators will improve administration/re-administration to ensure durable effectiveness. I would also expect that allogeneic cell therapies will be approved to treat a broad array of cancers.
A: For personalized medicine to become truly impactful, it will be critical to gain a picture of inherently heterogeneous diseases down to individual cells, since this is the only path to fully understanding their biology.
Today, cancer progression, treatment resistance, and disease recurrence are commonplace because we do not fully understand clonal evolution or heterogeneity, missed by bulk analysis. But single-cell DNA and multi-omic sequencing technologies allow us to see into individual cells.
These transformative analytical technologies will enable the development of cutting-edge therapies that can truly address cancer drug resistance, as well as devastating genetic diseases. Mission Bio’s partners have already made discoveries with our Tapestri platform that can change the way we understand and treat diseases like acute myeloid leukemia, pediatric myelodysplastic syndrome treatment, and solid tumors, to name a few.
In parallel, hundreds of personalized cell and gene therapies that rely on changes made to DNA in human cells are in clinical development but dogged by safety and efficacy concerns and regulatory delays. Here again, single-cell multi-omic technologies will be crucial for getting personalized therapies to patients by providing incredible insight into the heterogeneity of the engineered cells and therapies, allowing drug companies to fully characterize their therapeutics early in development, with implications for trials and ongoing patient monitoring.
Soon, we expect these same single-cell analytical technologies will play a recurring role in accelerating therapeutic development, improving cancer diagnosis, and identifying clonal progression, taking precision medicine to new heights.
A: At a macro level, I believe that personalized medicine can only become a reality upon adoption of a suitable social, regulatory, and economic framework. This will require innovation in the education of both staff and patients, reimbursement and regulatory practices, knowledge and data sharing policies, and practice management strategies.
The implementation of personalized medicine will also require updated manufacturing methods that allow for tuning of drug release kinetics based on an individual’s ideal dosage. One proof point is the emerging field of high-throughput screening of excipient and drug combinations, a market where we see increasing start-up activity. Another example are additive manufacturing technologies, such as 3D printing, for the oral delivery of tailored-dosage or multi-API pills. Aprecia Pharmaceuticals’ Spritam tablet for epilepsy treatment was the first 3D-printed pill to be approved by the FDA back in 2015. Now, leading science companies, such as Merck, are investing in drug manufacturing via 3D printing technology. Polymer science and expertise to engineer excipients that enable tailored drug release will be a critical success factor in this field.
Third, I observe strong growth in the 3D-culture market for rapid in vitro testing of niche therapies, for example in the field of oncology. Functional drug testing with culture systems, such as organoids or cell-impregnated matrices, might accelerate clinical screening to bring personalized therapies into reality. As an example, our NovaMatrix® business offers innovative ultrapure alginates that can be utilized as an extracellular matrix in this field.
Dr. Austin Mogen is a Senior Field Application Scientist at Corning Life Sciences. He received his doctorate from the University of Florida and gained industry experience as a Senior Scientist of upstream process development and manufacturing supervisor for viral vector manufacturing. In this position he focused on bioprocess development, closed system solutions for cell culture scale-up, and viral vector production. Since joining Corning, Dr. Mogen works extensively with academic researchers and process development groups, optimizing cell culture assays and cellular scale-up conditions for viral production, cellular therapeutics, and biologics.
Many of the change agents I have seen in 2019 are derived from changes in regulatory law, commercial downscaling, and impact from patent expiry strategies. The largest external regulatory change came from the issuance of the long-awaited EMEA Annex I, clarifying which technologies are required and acceptable, when and why.
The change in operational focus, from clinical scale-up to commercial scale-down, is enabling use of smaller, modular, flexible fillers with self-contained isolators. In parallel with the approval of biosimilars and biobetters, there is strong industry focus on individualized micro-batches, for CAR-T solutions and gene therapy products. The use of process automation and robotics have increased in all fill-finish unit operations. Widespread implementation of ready-to-use/ready-to-sterilize components and single-use (SUT) in upstream and downstream (SUS) through final fill designs have changed how facilities are planned, reducing plant size and changing warehouse space to accommodate densely packaged plastics goods.
Filling modalities have also been changing; bags that can be mated to lock-luer fittings with pre-sterilized needles and blow-fill-seal/form-fill-seal are re-emerging as processes that offer potential unit cost reduction. Traditional vial and syringe container designs are also changing as suppliers improve standardize offerings while having options including clear plastics.
The most exciting technological or scientific advancement that has influenced our business strategy in 2019 is our novel epigenetic regulator program. Unlike gene therapies, which target and modify DNA directly by inserting specific genes into patient’s cells, epigenetic regulators control or modify gene expression through processes that do not alter the sequence of DNA directly. Our lead asset DUR-928 is a small endogenous molecule that plays an important role in regulating cellular functions such as lipid homeostasis, inflammation and cell survival, crucial pathways involved in many acute and chronic diseases. DUR-928 has shown positive results in a phase IIa trial for the treatment of alcoholic hepatitis, a devastating acute condition with high mortality rates and limited therapeutic options. We are also advancing programs in other indications that could benefit from DUR-928, such as non-alcoholic steatohepatitis (NASH) or psoriasis. We believe that epigenetic regulation is a powerful and untapped treatment approach for many challenging diseases.