January 7, 2022 PAO-12-21-RT-02
A: With the approval of Zolgensma in 2019, a gene therapy for treatment of spinal muscular atrophy that impacts infants, we are ushering in an age where many difficult-to-treat genetic disorders have the potential to be cured. Two therapeutic areas where I expect to see great progress are for neurologic disorders and rare genetic diseases. Many technological developments have recently been made to enable the scalability of gene therapy manufacturing, such as the Corning HYPERStack® cell culture vessel and the Ascent Fixed Bed Reactor System. Improvements in both viral vector design and systems for gene therapy production are making commercialization of gene therapies a reality.
A: Therapeutic areas offer a convenient demarcation allowing us to focus areas of research to better understand and address disease. We look at solving problems by the conditions and areas of the body in which they manifest themselves: cardiology, the heart; dermatology, the skin; neurology, the brain; and the central nervous system. Oncology/cancer is different; it has always been a scary illness, stigmatized and, for much of history, too scary to name. Cancer is the body’s own cellular system gone awry.
Cancer is a genetic condition. It is not a foreign invader (although it might be triggered by one) but is caused by genetic mutations in our own tissues, possibly influenced by epigenetic factors, that manifest in uncontrolled cell division and disrupted biological processes. Many of the most advanced cancer therapies currently target a cancer’s genome to suppress its growth and spread.
But what about other genetic conditions: congenital ones like sickle cell anemia, muscular dystrophy, cystic fibrosis? Many of the same technologies employed to target cancer are also being brought to bear on congenital conditions.
Going back to the previously named therapeutic areas of neurology, cardiology, and dermatology, many diseases in these areas (Parkinson’s, Alzheimer’s, hyperlipidemia, plaque psoriasis) are being linked to genetic traits and epigenetic factors.
Perhaps the “therapeutic area” that could see the greatest progress will not be an existing area at all, but a convergence of the understanding of disease at a more fundamental level, allowing us to make advancements in many areas of therapeutic interest, all at the same time.
A: The pandemic has stimulated a renewed interest in all areas of therapeutic and biotechnology development, so this is a difficult question to answer. The area of expertise for our company is in the development of synthetic lethal cancer drugs. We would not be engaged in this field if we did not foresee this to be a therapeutic area in which we could make great progress within the near future. Synthetic lethal drug development is possible when the same cancer-associated changes that enable carcinogenesis also introduce an overdependence on specific proteins or pathways. Of course, finding these dependencies and targeting them with a drug is difficult. The most recognizable synthetic lethal cancer therapeutics in use are the PARP inhibitors, which have found use in cancers with DNA-repair deficiencies, such as those associated with BRCA mutations. Given the enormous success of PARP inhibitors and thus the synthetic lethal approach in general, we expect many more synthetic lethal cancer drugs to emerge in the coming years. This includes targeting newly uncovered dependencies that we have thus far not fully appreciated.
A: Respiratory diseases, such as asthma and COPD, continue to dominate the inhaled space, with COPD the third leading cause of death worldwide in 2019. These represent the majority of the inhaled targets for drug development, but, with the rise of biologics, we are seeing new classes of treatment emerge to tackle these diseases. With 80% of COPD deaths coming from low- or middle-income countries, further development of generic and lower-cost treatments will also be vitally important, and we hope to see continued progress in what can be a challenging area of development.
Beyond the traditional targets, we are seeing a rise in interest for other indications. Antiviral and antibiotic treatments for the lung are increasing in number, and we are seeing a lot of interest in nasal delivery of materials for systemic treatment of conditions like Alzheimer’s, depression, migraine, etc., with some exploring the potential for delivery to the brain through the olfactory regions in the nose. For example, the recent launch of a single-dose nasal DPI product that delivers emergency glucagon treatments illustrates the types of products that we may see more of as innovation and development in the area continues.
Vaccine delivery by inhaled and nasal routes has already been proven for flu vaccination, is an active research area, and has taken on new significance with the current COVID-19 situation. There has been an increased interest in nasal delivery, targeting an immune response within the mucosal regions of the respiratory system where the initial COVID-19 infection occurs. Having an effective local immune response in addition to a systemic response can significantly boost the potential efficacy of a vaccine. Nasal vaccines can provide other advantages, such as easier administration by people other than traditional healthcare workers as part of a widespread, needle-free, mass vaccination strategy.
A: The success of the COVID-19 vaccines has shown the potential of mRNA vaccines for prophylactic purposes. In coming years, I think that we will see rapid developments in mRNA to tackle other infectious diseases. In addition, we will also see the platform’s therapeutic use in oncology, for example, in combination with other therapeutic strategies, such as the use of checkpoint inhibitors. Another area of great interest for mRNA therapeutics is in gene therapy applications for treating genetic diseases like lysosomal storage disorders with a “protein replacement” approach. In these situations, the liver or another organ can be used as a “bioreactor” to supplement a critical protein that the patient is either not making correctly or not making in the necessary quantities.
To make full use of these technologies, we will need to ensure that the mRNA can be effectively and safely delivered into the cell. Lipid nanoparticles (LNPs) are crucial to the successful delivery of nucleic acid therapeutics, although other formulation platforms are currently being investigated as well, which will be complementary to LNPs, for example, by being able to target organs other than the liver.
A: Particularly for the treatment of cancer, both mRNA-based therapies and antibody–drug conjugates (ADCs) have potential for tremendous progress.
We've seen the noteworthy success of mRNA against infectious diseases over the last 18 months of the pandemic as a part of the COVID-19 vaccine, but applications in the field of oncology are still developing. As a modality, it's simple, elegant, and incredibly precise with the genetic sequence. As we've seen, because of the simplicity, it's incredibly quick to market. There will be significant investments and advances in mRNA as a modality moving forward. It will continue to go from strength to strength, especially given the proof of principle that it's safe and can be deployed on a huge global scale.
When it comes to an ADC as a therapy, it has the potency of a small molecule. Yet, with the delivery system, when it's attached to a monoclonal antibody (mAb), you have an antibody's precision and cellular focus. It offers the best of both worlds. You have the magic bullet effect of the mAbs and the potency of a small molecule API, so it will continue to be a very strong tool in our pharmaceutical armory.
A: Undoubtedly oncology. It is currently changing and evolving, thanks to tech platforms that record and combine data longitudinally with treatment information and outcomes as the cancer is being treated. The next step is to leverage the data to get insights, improve disease prevention, and add quicker, more effective drugs in the market. At SOPHiA GENETICS, we’ve recently highlighted two biomolecular approaches already being implemented within our technology that show great promise in aiding research for new therapies. These include the detection of homologous recombination deficiency (HRD) and RNA fusions (RNA targeting). Clinical studies are revealing how effective these types of biomarkers can be in not only identifying but also tracking the effectiveness of treatment for cancers associated with these molecular abnormalities. Precision medicine is all about further impacting clinical discoveries by fine-tuning the complicated process, something I believe will be accomplished with a data-driven medicine approach. At SOPHiA GENETICS, we supply researchers with the advanced data-driven tools they’ll need to support their drug, treatment, and research development.
A: One of the reasons I was drawn to Double Rainbow is that we take a disease-agnostic approach to our scientific platforms. As we look at the standard of care across many therapeutic areas, we unfortunately see that, for many diseases, patients are left with underwhelming options. While we hope to apply our technology through partnership to a wide range of therapeutic areas, what we see in the near term is a continued prioritization of oncology by much of the industry. Given the scale and devastating nature of many cancer diagnoses, it is reasonable to see significant investment in this area, and I believe the collective efforts of researchers and applications of novel technologies — like those being explored within Double Rainbow — will continue to revolutionize care for these patients.
In addition to oncology, there is a significant opportunity to advance the standard of care for people suffering from neurologic disorders, particularly neurodegenerative diseases such as Alzheimer’s, Huntington’s, or Parkinson’s. In recent years, we have seen several incremental steps toward improved care for these patients, but as our knowledge of biomarkers and mechanistic pathways continues to grow in combination with emerging technologies and novel modalities, researchers have an opportunity to push for meaningful, disease-modifying treatments for these patients. That is why our team at Double Rainbow is exploring multiple opportunities to advance the standard of care in this space through either enhanced drug delivery and targeting via our PRISM platform, or through novel asset origination via our HARMONY platform. Ultimately, our team is dedicated to doing whatever it takes to maximize our technologies for the benefit of human health.
Elliott Franco, Ph.D., Vice President, Laboratory Operations, Alcami
A: Pinpointing one therapeutic area is nearly impossible, as there is and will continue to be a tremendous surge of breakthrough therapies across oncology, vaccine, immunosuppressant, and other high-growth therapeutic areas. What is certain is the need for effective and efficient drug development cycles to maintain this extraordinary momentum. Alcami finds its niche here in our ability to foresee the needs of our customers, both in timeliness and capabilities to facilitate the progress of these advanced therapeutics.
As an established CDMO with a versatile service offering, we provide high-throughput method development, efficient protocols for method onboarding, and industry-leading performance metrics for GMP analysis. This platform allows us to select optimal parameters quickly and develop robust and QC-friendly methods that are established for testing in much shorter timeframes.
With great progress also comes the need for innovative technology to turn concepts into reality. Alcami continuously assesses and acts on what investments will deliver best-in-class drug development cycles. For example, we recently acquired analytical ultracentrifugation, variable pathlength UV for A260/A280 determinations, and new tandem quadrupole and QTOF instruments, as part of a 16,000-ft2 renovation in our Durham, North Carolina, laboratory to be commissioned in Q1 2022.
A: In the coming years, I believe we could see innovation in the treatment of diabetes via emerging technologies and therapies. Thirty-four million Americans — about one in 10 — suffer from diabetes, and it’s the nation’s seventh leading cause of death, with about 79,000 deaths attributed to the disease annually. I’ve witnessed firsthand through my wife, who has type 1 diabetes, how difficult it is to handle. Outside of insulin injections or eating candies and other foods high in glucose, it’s not easy to regulate one’s blood sugar. We must create a technology with a better closed-loop management system that can share feedback, manage these levels, and provide insulin or sugar when needed. Currently, no device gives sugar to those with diabetes, only insulin.
While significant progress still needs to be made in the treatment of diabetes, Vertex Pharmaceuticals’ stem cell–derived diabetes therapy, VX-880, has the potential to create substantial change for those living with the disease. When the body’s blood sugar is too high, this system can deliver insulin to lower it, but when it drops too low, it offers glucose to raise it to a normal level. The therapy has already seen impressive results from its phase I/II clinical trial. The first patient who received the therapy saw their need for insulin disappear, providing hope of finding a sustainable treatment for the currently incurable disease.
A: I believe that we will see great progress in cell-based immunotherapies for oncology indications in the coming years. With the deployment of five CAR-T cell therapies approved for clinical use, the field has now developed a path for clinical translation and commercialization of this new class of therapeutics. Motivated by these successes, there has been a great expansion in preclinical programs that are quickly advancing to the clinical track. Many of these are aimed at addressing the vast unmet need for treatments against solid tumors, and we hope to see these initiatives translate into improved outcomes and cures for this critical patient population.
A: Historically, the best metric for advances in a therapeutic area follows either advancement in the understanding of the biology of the disease state, a large unmet need in public health, or both. In tracking with recent advancements, the area of inflammation has shown great strides in understanding the underlying causes of physiological responses that then trigger inflammatory cascades and ultimately symptomatic disease states. Conventional therapies have targeted these symptomatic responses to inflammation, but, with this new understanding, we can expect to see great progress in the treatment of the causes of inflammation response, hopefully even before symptoms become problematic. This will lead to new therapies targeted to change how asthma/COPD, arthritis, and autoimmune diseases are treated and a call to design and develop more targeted large and small molecule therapeutics. The advent of new therapeutics will require innovation in the synthesis and route design of these more complicated medicines as well as integrated development with new drug delivery technologies.
The COVID-19 pandemic has exemplified how extreme public health needs will drive rapid and innovative progress as well. We have already observed new therapeutic approaches to vaccines in the design of the therapy as well as the integrated drug delivery system. This will continue to drive innovation and change, and we will be ready to meet these challenges as we see them on the horizon.
A: Cancer immunotherapy with mRNA-based vaccines. Multiple clinical trials for such therapies are currently being conducted, and the successful use of mRNA vaccines for COVID-19 has given the development of mRNA-based cancer vaccines a significant boost.
Mahsa Mohiti-Asli, Ph.D., Technical Manager, BASF Pharma Solutions
A: The first wave of personalized medicine caught oncologists’ attention to use this technology in cancer therapeutics. The complexity of cancer cells, along with different somatic mutations, complicates the diagnostic and treatment plans. Historically, cancer patients have been treated with radiation and some cytotoxic agents that kill tumorous cells and healthy cells at the same time. This approach results in known severe side effects, such as hair loss, nausea, and fatigue. It is also often not very effective.
More recently, immunotherapy has shown great promise for cancer treatment. This therapeutic approach attempts to give a patient’s immune system information that enables them to recognize and destroy cancer cells in a selective manner. In other words, your immune system is trained to be selective and not attack normal tissue and cause side effects. Individualized therapy in cancer treatment can be used to understand all the mutations that are present in a patient’s tumor, to forecast which of those tumor-specific mutations are going to be important in the generation of an immune response, and to predict the immunogenic neoantigen as part of the patient’s therapy.
These days, modern genomics techniques let us map a patient’s tumor mutation profile. These analog data can be converted to digital data and used in predictions of the mutation profile of a specific patient using artificial intelligence (AI). The scientific advances in individualized cancer therapies bring enormous hope for more effective therapies with less severe side effects in this area. The digital methods also offer a more reproducible — and thus scalable for production — workflow.
James Peterson, Global Vice President, Pharmaceutical Ingredients, Univar Solutions
A: Innovation is accelerating in therapeutic areas that traditionally receive significant funding. Not surprisingly, these areas — oncology, cardiovascular disease, diabetes, and infectious diseases — will likely see great progress.
When we consider advancements in treatments for infectious diseases, we think about the progress in biopharmaceutical treatments linked to the pandemic. We’re witnessing a propelled focus in this space — the point where biotechnology and pharmaceutical manufacturing meet — as scientists seek answers to quickly treat and even prevent deadly infectious diseases like coronavirus disease (COVID-19). Rather than synthesizing chemical compounds to produce an active pharmaceutical ingredient that treats a symptom, biotechnology uses living organisms or components of living organisms to help an individual’s own genetic makeup fight or prevent disease. This technology isn’t exclusive to COVID-19 vaccines and therapies. Biopharmaceutical organizations are using biotechnology to treat therapeutic areas such as cancer, cardiovascular disease, and other illnesses.
Serving the biopharmaceutical industry has offered Univar Solutions the opportunity to demonstrate the value of our robust distribution capabilities, including supplying ingredients used in COVID-19 vaccine production. As biopharmaceutical treatments continue revolutionizing medicine for other therapeutic areas, we’re supporting customers with our expansive and diversified portfolio, building out our infrastructure, and providing manufacturers ready accessibility to the high-purity solvents, excipients, and other ingredients they use to produce treatments aimed at keeping our communities healthy and safe.
A: Oncology and rare diseases are the therapeutic areas where I believe we’ll see the fastest and greatest adoption of precision medicine. For rare diseases, the need is so great, with long research discovery cycles but precise due to molecular/genetic testing (e.g., genotype and phenotype). In oncology, the adoption will be driven by the very rapid understanding of biomarker impact on disease progression and therapeutic options for treatment.
However, we do need to (a) incorporate clinical trials as a care option to provide more choices to treating physicians and their patients and (b) expand clinical trials from being limited to a small set of healthcare organizations as trial sites to a broader range of sites in all communities and geographies. By doing this, more diverse populations will be served, the movement to precision medicine will continue at a rapid pace, and we can better support studies which are challenged today, because limited patient recruitment is stalling research.
A: There are two areas where we’ll likely see the greatest progress: oncology and vaccines.
There are going to be major advances in some of the hardest-to-treat cancers. For example, bladder cancers will be beneficiaries of both broader use of immuno-oncological therapy and more targeted therapeutics. They’ll be treated with the precision and narrow patient stratifications based on genomics now standard in non-small cell lung cancer (NSCLC). We’ll also see substantial improvements in outcomes, treatment durability, and quality of life.
Multiple myeloma and other hematological malignancies will also move into a new era of options. More effective treatments will be available earlier, and late-stage (e.g., triple class refractory) treatments, such as CAR-T and other engineered cells, will assure longer survival and far great quality of life for broader groups of patients.
Looking at vaccines, the COVID-19 vaccine development process validated mRNA approaches as safe and precise for vaccines. This has the potential of revolutionizing where and how vaccines can be deployed economically, with speed and precision.
A: It’s inspiring to see notable progress across the healthcare industry and its many therapeutic areas. I’m particularly excited about current advances and what’s to come in ophthalmology, as innovations in drug delivery — most notably those offering extended therapeutic delivery — have the potential to shift treatment paradigms toward greater efficiency, improve patient adherence and compliance, and continue to maximize safety and effectiveness.
Extended-release drug delivery options that require less frequent administration — be it at the doctor’s office or at home — may offer a comparatively longer duration of effect in addition to more consistent and balanced therapeutic delivery. This sort of optimization will serve to benefit the patient, caregiver, and healthcare provider alike in meaningful ways — for example, patients may not need to see their doctor as frequently for an injection or be required to administer as many eyedrops in a given timeframe.
Collectively, all of these factors — minimizing invasive procedures and offering more convenience, coupled with safe and efficacious therapeutics delivered over a longer period that maintain a stable level of vision and less deterioration of eyesight — hold the power to help reduce treatment and disease burden on the patient and further improve outcomes. Promising headway in this space is already being made, and I’m extremely optimistic about the transformative advances we’ll see in the next few years.
A: Monoclonal antibodies will be the therapeutic area with the greatest progress throughout the coming years. Antibodies are proteins created by the human immune system to fight against disease. Recent advances in our understanding of biology have led to great therapies in oncology, such as checkpoint inhibitors, and, more recently, neutralizing antibodies against COVID. There are now multiple novel ways of using monoclonals, including in cocktails, combinations, and against novel targets to create therapies that are safe and highly effective.
Historically, monoclonal antibodies have been utilized in the treatment of cancer. While cancer will continue to be a target of antibody therapeutics, the emergence of COVID-19 has shown that monoclonal antibodies are highly advantageous in the fight against infectious diseases as neutralizing antibodies (nAbs). This is due to their ability to home in on specific epitopes on the virus, such as the spike protein, to neutralize the virus directly. The net effect is much higher efficacy and safety compared with other treatment methods.
At Abpro, we have developed an entire program for COVID-19 based on neutralizing antibodies. ABP310, which has the advantage of being future-proofed against variants yet to come and has superior binding to the SARS-CoV-2 spike protein than currently approved nAbs, which enables it to be used very effectively as a therapy and also as a prophylactic for immuno-compromised individuals who can't generate a response to vaccines. Our antibody treatment binds to areas of the spike protein that have not changed over multiple generations of viruses so that it will remain effective against future variants.
As the pandemic continues into 2022, vaccines will be critical in quelling the effects of the pandemic. However, a one–two punch will be required in order to complete the puzzle as a treatment for breakthrough cases, immunocompromised patients who cannot develop their own antibodies in response to the vaccine, and other non-responders or non-adopters of the vaccine.
A: Our greatest impact will be in the field of psychiatry, due to our bringing a precision medicine approach to the field for the first time. Today, psychiatric treatment only works for roughly one in three patients. Core to this problem is the challenge that we can’t identify who those one in three will be. Current diagnoses are based on clinical symptoms only, without biological biomarker tests that direct any aspect of diagnosis, prognosis, or treatment selection in psychiatry. Consequently, medications and devices are developed using a one-size-fits-all approach. By contrast, other therapeutic areas have leveraged precision approaches and generated far better results for patients. As a consequence, the total investment in precision medicines has risen rapidly in recent years. Now is the time for a precision approach in psychiatry. Doing so would generate rapid progress in a space that hasn’t seen innovation in decades. We are poised to rethink how we diagnose mental health conditions and to begin developing personalized treatments that are geared toward likely drug responders, taking the guesswork out of psychiatric treatment. In the coming years, the expansion of precision psychiatry, an emerging field that takes an individual’s brain biology into consideration, will likely see tremendous progress, because the current global state of mental health demands this progress. By combining artificial intelligence with data from behavioral tests; brain function measures, including electroencephalography activity; and wearables, we will be able to optimize treatments for patients that actually work for them because of their targeted nature. Consequently, by moving away from the trial-and-error approach that pervades psychiatric drug development and clinical practice today, the lives of those with mental health conditions will dramatically improve.
A: Technological innovation, and particularly fields like artificial intelligence, have opened up new potential in cancer treatment. The emergence of immunotherapies, small molecules, and other therapies has increased overall survival and made it possible to address more cancers that are not responsive to chemotherapy or radiation. The next step in oncology research is to identify new solutions for the patients that are still being left behind — that is, the many patients who have cancer driven by less common mutations that are more difficult to treat. I am encouraged by the motivation and growing capabilities of the scientists whose aim is to address these rare cancers, including our team at Fore Bio, and am optimistic that within the coming years we will see the beginnings of a new model of precision oncology where treatments are hyper-targeted and therapeutic strategies are personalized for every cancer patient.
A: Technology that enables us to reach a new future of precision medicine expands across many therapeutic areas, but, as CEO of an oncology company, I am particularly excited about our industry’s potential to make additional progress in cancer treatment in the coming years. The scientific community has continued to rally behind the discovery of new ways to drug important pathways and new insights into mechanisms of drug resistance that can lead to next-generation therapies or unique combination strategies. This has sped up our ability to pursue hypothesis-driven therapeutic approaches and thus expanded the total treatments in development.
The sheer amount of ongoing innovative cancer research right now is incredible and will hopefully have a positive impact on patients who do not respond to or become resistant to current therapies. Each new mechanism identified is a new potential pathway for a cancer patient to find a cure. Personally, I am optimistic for a future where cancer treatment is more tailored to each individual, guided by the continual knowledge-building across the oncology research community and our shared passion to find viable treatment avenues for every person living with cancer.
A: Among experts, the conversation is not about if there will be another pandemic, but when it will occur. The focus of these conversations surrounds the global emergence of antimicrobial resistance (AMR). Notably, no new classes of antibiotics have been brought to market in decades, and, with a long history of overuse and misuse of existing antibiotics, physicians are left with limited therapeutic options for patients when faced with AMR. The World Health Organization has recognized AMR as the cause of over 700,000 deaths worldwide and estimates that this figure will likely increase to 10 million by 2050. This urgent need has sparked significant investment and research in the space. New classes of anti-infectives have shown efficacy in clinical trials against some of the most resistant bacteria, including a designated group of nosocomial pathogens commonly associated with AMR, acronymically dubbed “ESKAPE” pathogens due to their propensity for “escaping” the biocidal action of antibiotics. ESKAPE pathogens, which include both Gram-positive and Gram-negative bacteria, make up the majority of multidrug resistant infections. The research and development of new classes of anti-infectives will no doubt see extensive progress in the coming years as the world continues to advance the fight against deadly drug-resistant pathogens.
A: I believe that we’re entering an incredibly exciting time in the field of precision therapy for genetic cardiovascular diseases. We’ve known the genetic causes of several major inherited heart diseases for decades, but the field has been limited in the therapeutic tools at our disposal to correct the underlying disease biology. For instance, the first genes implicated in long QT syndrome and hypertrophic cardiomyopathy were identified in the 1990s, but precision therapies for these types of disorders have only recently become feasible.
Today, we’re getting closer than ever to having the right set of technologies to address the underlying disease biology of many different genetic heart diseases. As clinical, genetic, and disease biology insights for many of these diseases continue to advance and become more sophisticated, we’re able to pair these insights with emerging therapeutic modalities that have tremendous potential.
AAV-based gene transfer is an excellent example of how far this field has come. With AAV-based gene transfer, we now have the potential to bridge the gap between knowing how several genetic heart diseases unfold and knowing how we could effectively treat them to address their mechanistic underpinnings. These advances in precision therapy could allow us to help patients living with chronic and devasting genetic heart diseases, such as dilated cardiomyopathy, like never before. I’m hopeful that, in the coming years, we’ll continue to witness some profound advances in this field.
A: Biotechnology-based treatments are helping fight some of today’s most life-threatening diseases and are bringing promise to several areas of therapeutics, so it is hard to pick just one.
The advances we have seen in immuno-oncology are impressive, and I anticipate that this therapeutic area will continue to see a great deal of progress. With another treatment area, cell and gene therapies, any genetic disorder can potentially be treated. Both of these treatment areas have the potential to collide and produce fantastic results.
For example, today’s typical recombinant protein–based treatments (like monoclonal antibodies) are helping turn cancer into a chronic disease that doesn’t end life prematurely. We have seen tremendous progress here and will continue to see more in the coming years. In addition to these advances, there are cell and gene therapy oncology treatments being developed that have the potential to cure patients altogether.
We are still at the beginning of the cell and gene therapy revolution, and some of the treatments require early detection to make an impact on patient lives. Therefore, diagnostics is a third area we cannot forget. It is necessary to advance rapid and cheap genetic diagnostic testing in newborns and young children to avoid the development of some pathologies.
AGC Biologics is currently working with more than 100 processes that will treat or cure multiple diseases, and we anticipate exponential growth in treatments of life-threatening diseases coming to market that will improve the lives of millions of people.
A: I think that precision medicine will be spearheaded by the field of oncology, where the need for accurate diagnosis, therapy optimization to unique pathophysiological factors, and disease progression monitoring are indispensable for successful treatment. We see that the industry is making significant investments in the relatively small,but rapidly growing fields of cellular therapies and regenerative medicine. To illustrate, cellular immunotherapies based on T cell receptor, CAR-T cell, and NK cell platforms show potential for differentiated cancer treatments. The Alliance for Regenerative Medicine reported a surge in investment in this field, reaching $6.6 billion in the first half of 2021.
On the other hand, I would recognize the significant challenges that the industry is still facing to implement precision medicine in large therapeutic fields, such as diabetes. With a large patient pool available for data analysis, treatments are already tailored to the patient on the basis of population averages. However, treatment at the individual level is still challenged by factors such as data-collection and data-sharing restrictions and by the implementation of a flexible and decentralized supply chain. In addition, one can question the balance between new healthcare delivery practices and patient empowerment.
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.