Scientist (formerly Assay Depot) is a San Diego-based software company that is pioneering a new approach to scientific research. The company runs an online research marketplace that enables scientists to quickly and cost-effectively translate their ideas into experimental results.
Guest blog written by Sasidhar Murikinati, Ph.D – Genscript
Therapeutic antibody drugs have recently experienced explosive growth due in large part to the fact that immunotherapies stimulate the immune system to attack cancer cells. Within oncology research alone, more than 20 therapeutic antibody drugs received FDA approval for new treatments or indications during 2015 to 2018. Additionally, more than 300 therapeutic antibody drugs are in ongoing clinical trials.
Bispecific antibodies are emerging as a novel approach for immunotherapies by combining two antigen-recognizing elements into a single construct that is able to simultaneously bind to two distinct targets. They can be applied to recruit immunological effector cells for killing tumor cells or to simultaneously block two signaling pathways or cytokines. Subsequently, they have prompted significant interest for a number of therapeutic applications, both in cancer and in other indications. The growing interest in therapeutic antibodies along with the rapid progress in antibody engineering have yielded a multitude of bispecific antibodies formats and derived molecules that differ in size, shape and function, sometimes referred to as a “Bispecific antibody zoo”. These bispecific antibodies can offer additional advantages:
Provide superior potency due to novel mechanism of action
Offer enhanced safety profile due to less off-target binding & lower dose – as seen in safety concerns in combination therapies
More cost-effective as it only develops one molecule and saves half of investment in comparison to combination therapy
All these advantages of bispecific antibodies make them potential powerful treatments for patients and physicians. However, despite the numerous bispecific formats and benefits they have brought to patients, there are two major challenges in developing them:
Over-engineering of naturally generated antibodies may lead to an antibody therapeutic to produce its own immune response, making the drug ineffective.
Commercially generating bispecific antibodies can have manufacturing problems due to their non-natural format, such as product instability, low expression level and complex purification process.
With these two major concerns in mind, Genscript has developed the SMAB bispecific format, which is a single domain antibody fused to a monoclonal antibody. The concept is very simple in that we will use all-natural components to realize bivalent and multivalent purpose. The major advantages with the SMAB platform are bio superiority, excellent developability for high yield and stability. SMAB Bispecific Antibodies demonstrated high affinity to the target cells in many models. In addition, the SMAB platform has several advantages over mono-specific therapeutics and other bispecific antibody designs, including:
BsAbs show bio-superiority and a better safety profile over monotherapy or combinatorial therapeutics
SMAB platform has good developability and therefore can generate high yields & concentration in formulation with desirable stability
the SMAB platform has the same manufacturing process as conventional antibody therapeutics
the sdAb in GenScript’s SMAB platform has the ability to bind to “hidden” epitopes, such as enzymes, ion channels, etc. as well as being highly flexible for the construction of multi-valent molecules using a “plug and play” fashion.
Amidst fierce competition coupled with many unmet medical needs, there is an urgent demand for new therapeutic strategies, such as combination therapy, and novel modalities, such as bispecific antibodies. In this interactive webinar, Genscript gives an overview on therapeutic antibodies, opportunities and challenges of current monotherapies and major benefits of bispecific antibodies and platforms.
Webinar - Bispecific Single-Domain Antibody fused to Monoclonal Antibody (SMAB): The Natural Form - YouTube
GenScript serves as a partner for researchers in basic life sciences, translational and biomedical fields as well as early-stage drug development. With best-in-class capacity and capability in both technology and manpower, GenScript supports scientific endeavors through offering high-quality products and services. The diverse portfolio of GenScript encompasses extensive services in gene synthesis and molecular biology, peptide synthesis, protein expression and engineering, custom antibody development and engineering, animal model development, in vitro/in vivo pharmacology as well as variety of catalogue products. With the goal of “Making Research Easy”, GenScript has strived to remain a reliable research partner for scientists in over 100 countries across the globe.
Breathtaking progress in life sciences has brought us innovations such as high-throughput and individually affordable genomic sequencing as well as next-generation flow cytometry that can phenotype dissociated cells for their expression of dozens of markers simultaneously. The development of cutting-edge technology solutions with standardized workflows has led to increased efficiency and reliability for these and other cell-based techniques.
Understanding how populations of cells in the native tissues they form are altered in disease states is an equally important venture and unfortunately is one that has seen relatively little in the way of breakthrough technology development in recent decades. Specifically, the classical histology workflow centered around the equipment shown in Figure 1 is still in widespread use today in academic labs, biopharma companies and healthcare centers. This process involves:
Cutting tissue into thin sections, typically ~35-40 µm thick (but down to ~3 µm, which can require paraffin embedding)
Mounting the sections onto glass slides (and performing subsequent deparaffinization)
Labeling these sections with classical stains or antibodies,
Visualizing the sections either in their entirety at low magnification or by investigating discrete regions of interest (ROIs) at higher magnification
Figure 1: Traditional histology workflow involving an array of laboratory devices in which tissue samples are embedded in paraffin, sectioned into thin slices, mounted onto glass slides, de-paraffinized, labeled with stains and/or antibodies, cover-slipped and then imaged using standard light microscopy approaches.
More recent advances in optics and camera technology have allowed researchers to store microscopic images for offline analysis, and similar developments in fluorescence detection methods have facilitated automated analysis of signals of interest. Thanks to confocal microscopy and 2-photon excitation it has also become possible to extract some limited 3D information from thin slices and somewhat larger tissues (up to ~0.5-1.0 mm thick), although labeling is precluded in the latter especially when using higher molecular weight reagents such as antibodies.
However, the early part of the histology workflow, before the images are acquired, has remained fundamentally the same for some time, with tissue still needing to be thinly sectioned for it to be labeled and visualized. While multiple samples can be sectioned at once and then batches of slides can be stained in parallel by incorporating a bit of automation, this process has remained:
Laborious: human control is required for sectioning & mounting of the tissue
Error-prone: sections can be damaged or lost during handling
Inefficient & expensive: large quantities of labeling reagents can be needed to batch-process large numbers of slides, like those generated from sectioning an organ such as a mouse brain from end to end
Slow: labeled sections are imaged individually and then handled separately
Further, in this traditional workflow, classical stains and especially immuno-histochemistry only label the most superficial regions of the tissue. This reality, along with the limited penetration depth of light into tissue as it has typically been prepared, are together the main reasons why tissue sectioning is performed. Additionally, because it is prohibitively time-consuming to image the entirety of a set of sections comprising a given sample/organ, the results produced from this workflow often rely on sampling principles that can introduce inaccuracies or cause intra-area differences that are biologically meaningful to be missed.
Tissue-Clearing, a 21st Century Approach to Histology
Figure 2: LifeCanvas’s 21st century tissue-processing pipeline replaces traditional histology workflows, which involve a multitude of distinct steps and pieces of equipment (Figure 1), with a streamlined approach comprised of just 5 easy steps involving 3 turn-key devices and 2 simple solution kits.
In the past 10 years, however, and especially since introduction of the CLARITY technique in 2013 (Chung et al., Nature), a revolution has occurred in the field of tissue processing that has catapulted the discipline into the 21st century. Today, thanks to the chemical engineering-inspired approaches of CLARITY and more recently of SHIELD (Park et al., Nature Biotech, 2018), thick tissue samples the size of intact rodent organs and beyond no longer need to be meticulously cut into hundreds of sections to enable imaging and even labeling to take place. By preserving samples to withstand removal of all lipid-filled cell membranes ‒ which scatter light ‒ from the tissue, the samples can be rendered translucent in a process called delipidation that involves detergents and electrophoresis. Following delipidation of a sample and its subsequent incubation in a solution that raises and homogenizes refractive index throughout the tissue, the sample becomes optically transparent and can be imaged in its entirety while completely intact and un-sectioned. To learn more about these techniques, please visit LifeCanvas’ Technology page.
In addition to offering researchers a new and valuable perspective on histology, this 21st century tissue processing workflow requires dramatically less hands-on time vs. traditional sectioning-based approaches. Using the products below in LifeCanvas’s end-to-end, sample-to-dataset pipeline (Figure 2), entire rodent organs can be (1) SHIELD preserved, (2) delipidated, (3) actively labeled with antibodies & other molecular probes, (4) refractive index-matched and (5) light-sheet imaged at single-cell resolution, all with minimal user intervention and with labor requirements that are a fraction of traditional histology workflows.
With LifeCanvas’s pipeline you can not only simplify your workflow, but also take advantage of the power of whole-sample methods to:
Reduce processing work and view samples in multiple anatomical planes
Localize regions of interest more confidently by visualizing organ-sized datasets that provide greater context
Acquire data on all sample regions in parallel, facilitating analyses that are more quantitatively robust
Explore fertile ground where novel and unexpected discoveries can take place
LifeCanvas Technologies | Founded by CLARITY (Nature, 2013), SWITCH (Cell, 2015), and SHIELD (Nature Biotechnology, 2018) inventors from MIT and located in Cambridge, MA, LifeCanvas Technologies develops and offers as services a full suite of research tools for tissue clearing, labeling, and volumetric imaging of intact organs such as the brain. We are excited to show the biomedical research community the power of our whole-sample analysis methods, which provide greater value and richer information content versus traditional thin-section techniques, all at a competitive price.
In Part 1 we examined the evolution of outsourcing in drug discovery. In part II we will examine with deeper focus the specific reasons why it is beneficial to outsource scientific experiments. Research organizations and even individual researchers outsource for a variety of reasons, but here are just a few:
Access to innovation. As examined in part 1, the industry has evolved. In-house resources have in many cases shifted, meaning certain departments or services are no longer being offered. Many times, it is also a case of technological advancement. In early stages, novel technologies can be so cutting-edge that the tech isn’t readily available in a variety of places. This means that researchers often have no choice but to outsource parts of a project. If a new technology is developed that only exists with one innovative CRO or supplier, the choice is simple: either outsource through them or don’t use the technology. No one company has a monopoly on good ideas; therefore, as ideas and technology are developed globally, anyone who wants to access this expertise must outsource (or potentially license the use of the technology).
Strategic focus. Often referred to as focusing on core competencies, this basically means that a research team will work on what is likely to provide a competitive advantage or differentiator. The team can then invest its time and effort in making that as good as it can be while outsourcing the standard processes and experimentation to companies who have made that competence a core focus. This has the added benefit that time management within a research organization is not focused on marginal improvements or issue resolution in an area that is not strategically important.
Expense efficiencies. Accessing the global marketplace to take advantage of lower costs is often the first thought when organizations consider outsourcing. Regional wage rate differences, effective capacity, process optimization and economies of scale all play a part in outsourced services often being much less externally than conducting the research internally. Can we source? Even if we can use ourselves as a source, I think that would be good. But a 3rd party source would also lend credibility.
Speed. Accessing the pool of resources available in the marketplace will invariably mean that organizations will be able to shorten the lead-time for their overall research plans. Internal resource constraints, project prioritizations and bottlenecks can slow research down considerably. By utilizing CROs, companies can often select from a pool of options rather than relying on a single department to service the needs of their research projects. With peak-year sales potentially reaching in the billions of dollars and with a fixed and finite patent life, saving a few months in the product research lifecycle could equate to millions of dollars in additional revenues. From the perspective of CROs, since they often specialize in a particular technology or research area, pivots and shifts come much easier than with a large, less nimble research organization.
Flexibility. The ability to change focus as new opportunities arise (either through technology evolution or market changes) is greatly improved by utilizing a well implemented outsourcing strategy. As the research is conducted outside of the organization, companies can turn the taps of demand on or off quickly to re-prioritize without the time, effort and money needed to change course within the organization. Changing scientific focus in an internal team may take months as you hire or re-train staff, invest in capital expense, as well as manage the internal politics that often surround such changes.
In terms of which one of the above mentioned reasons to outsource is most important, this is often dictated by the current context for the company concerned and their strategic aims during that period. In a particular company the reasons to outsource may change over time, and the amount of volume spent externally will also flex based on the individual views of the leaders.
Regardless of the reasons for outsourcing there is no denying that it promotes innovation. Case in point, the relentless search for medicines to help improve patients’ lives is leading to innovations of all types occurring at an unprecedented rate. As we learn more about the various therapeutic areas and harness the power of data collection and processing, imaging, cell physiology, proteomics, just to name a few, it is impossible for pharma and biotech companies to retain this knowledge. Innovation is happening everywhere and accessing innovative services has become standard practice across the industry. The challenge today is not the decision to outsource – this is a given, rather it is the speed and manner in which companies can find the best innovation and access it that is becoming a competitive advantage in its own right.
So, what does the future hold for outsourcing? Looking at the new companies that are emerging within the life sciences, fewer and fewer are making the decision to invest in significant in-house lab space, preferring to follow a more virtual research model. Based on a recent report, there is reason to believe this will continue into the future, and as we watch these companies grow there will be some truly significant ‘virtual biotech’ companies. The continued advancement of IT capabilities will further serve to make this transition to ‘super virtual biotech’ smoother over time.
The Big Pharma companies have over the years may have reduced the amount of internal research, but the goals remain the same: focusing on innovation and discovering drugs to bring to market that cure illnesses. Continued change will be dependent on both the challenges faced by the individual pharma companies and the research leadership’s bravery to change, or disrupt, the status quo.
A recent white paper was released that traces the trajectory over the last ten years of 120 independent for-profit startups in the field of research workflows and scholarly communication. The author, Yvonne Campfens, presented the report at the Academic Publishing in Europe (APE) Conference held January 15-16, 2019 in Berlin. Campfens began the study with three main research questions:
Do the startups still exist (independently) in 2018?
If so, how were they funded and how are they doing?
If acquired by 2018, by whom and when were they taken over?
Established in 2007 in an effort to disrupt and improve ‘research workflows,’ Scientist.com was included in the study, which prompted us to reflect on how the outsourcing model, as a key component of the research workflow, has drastically evolved in the past decade.
To say the last 10, much less 15 or 20 years have seen a continual evolution in organizational outsourcing strategies by pharma and biotech companies is an understatement. One could even say that the outsourcing landscape has not only changed immensely over the last two decades but appears to be nowhere close to slowing down.
Outsourcing as a business strategy was not really discussed until the late ’80s, and the world of drug discovery was by no means an early adopter, especially when it came to R&D. At the time, traditional research organizations were vertically-integrated, brick and mortar spaces where a majority of the research activity was housed within the walls of drug discovery companies looking to secretly gain a competitive advantage.
The changes in the broader biotech industry have been well documented, with large pharma struggling to meet the challenges of a drug discovery pipeline capable of addressing looming patent cliffs and sustaining future growth. As a direct result, the specialized biotech and startup model received a huge boost. Rather than build out a full suite of in-house research capabilities, the majority of these companies focused on a few innovative, tech-driven capabilities. This gave them a competitive edge while utilizing external, third-party organizations to complete the remaining steps necessary to progress their assets to market.
With that being said, the explosion of science-based companies focused on highly innovative science is not restricted purely to drug discovery companies. The global contract research organization (CRO) network has seen massive growth as well. In fact, an article published in 2018 states that the CRO market is predicted to reach $44.4bn by 2021. So, not only has there been an emergence of big CROs offering a wide range of research services to pharma and biotechs, but there are also now thousands of smaller suppliers offering exciting new opportunities for creating better and faster science.
Never before have we had the breadth of scientific talent that we do today, but at the same time the scientific focus of this group has never been so broad, meaning that the experts in particular fields can vary widely in number. While many of these experts still undoubtedly reside in big pharma and big biotech, the culture of entrepreneurship and innovation that currently envelops our industry means that many individuals (and the number is growing) want to sit outside the confines of a large corporate environment and work independently. R&D downsizing, coupled with redundancy from mega-mergers and the rise in the propensity of universities to create spin-outs at impressive rates has thrust many would-be ‘corporate scientists’ into the world of the start-up, further enriching the pool of scientific excellence that is accessible to drug discovery companies on an as-needed basis.
Rapidly changing technology and innovation in the industry means that investing in capabilities becomes fraught with risk. An investment can become obsolete very quickly as new and more advanced methods arise. This is a major reason to access expertise from throughout the CRO network rather than self-invest. The network will maximize utilization of new technologies or platforms for multiple clients, amortizing the expense across channels and clientele. Furthermore, when a new technology is uncovered, CROs will incorporate this into their portfolio or drug developers migrate toward CROs with the new technology, thus having constant access to the cutting-edge innovations without the risk and expense of investment.
In Part II, we will examine the specific reasons and benefits of why individual researchers and research organizations are choosing to outsource scientific services.
Unlocking research potential through sample visibility
There are hundreds of thousands of human samples currently stored in the UK; the research questions they could address are endless. It has been well documented that human samples are excellent experimental models; their use early in drug development can decrease the risk of failed progression into Phase I and II trials. Research into precision medicine will further amplify the need for human samples in biomedicine. It is becoming obvious that using human tissue derived from donors will lead to better science; thus, their value to research is clear. But where are all these samples and how do we unlock their vast potential?
Why the mystery?
Although these many samples exist, it has been challenging to access and use them in research for a number of reasons. Predominately, the majority of researchers simply do not know where samples are located. Samples are stored in a variety of biorepositories including research institutions,hospitals and biobanks. Each of these storage facilities will have a different data system and standard, varying from excel sheets to databases. There’s also inconsistency in what data is available between organisations. For the samples to be useful in research, researchers will need data on the sample, the patient it was taken from, the treatment and storage of the sample, the consent and ethics/governance that applies to its use, as well as any study-specific information. Therefore, the key to unlocking these samples is to unlock the associated data.
Making samples visible through data
The UKCRC Tissue Directory and Coordination Centre (TDCC) was set up to address many of these issues. In 2016, we launched the UK’s first cross disease sample directory. To date we have better characterised over 180 sample resources, hosting over 400 sample collections, covering 136 diseases. This data is now all compiled in one open access, freely searchable database: the UKCRC Tissue Directory. Researchers can search by gender, age and disease or find resources that can acquire bespoke collections. This was achieved through the introduction of a data standard, which means that it is easier to pool data from different sample resources.
In addition to the unlocked power of the samples, the sample resources themselves remain an untapped infrastructure. There are over 300 existing human sample resources in the UK, from longitudinal cohorts to disease-based biobanks to bespoke collections services. These are embedded in a clinical environment and often have years of experience working with researchers, clinicians and pathologists. They can help researchers decide which conditions samples should be processed in, what associated data the researcher may need to answer a specific research question and they may even be able to offer help in experimental or assay design.
Accessing quality ethical samples
Once researchers have identified samples or resources that may be of use to their research, what’s next? Their own institution will have rules and regulations about what they will and won’t allow research to be conducted on. There are many layers of governance that applies to the use of samples in the UK. Furthermore, since the UKCRC TDCC is unable to audit the registered resources for quality control purposes, it is worth having a mechanism in place to make sure the samples are suitable for your work.
I recently had the pleasure of serving on a panel discussion as part of a webinar titled HEOR & RWE: Global Sourcing Strategies and Best Practices. Other panelists included Patti Peeples, RPh, PhD, CEO HealthEconomics.Com and Mary Beth Ritchey, PhD, Director, Epidemiology, Medical Devices & Real World Evidence, RTI Health Solutions. As the discussion moved to the Q&A portion, the main topic the audience wanted to hear more about was regulatory trends. Basically, as research organizations continue to conduct more RWE studies and utilize more real-world data (RWD), what changes can we expect to see from regulatory agencies?
Since RWE is not new, regulatory agencies have been using it to continually monitor the safety of products once approved in the market.
Firstly, let’s discuss what regulatory activities currently take place around RWE. Since RWE is not new, regulatory agencies have been using it to continually monitor the safety of products once approved in the market. Monitoring comes in the form of post marketing authorization studies, post authorization safety studies, risk management plans, etc., which are important factors in a product’s value story and risk benefit profile. But the question remains, can RWE be utilized even more in the regulatory approval process, and if so… what can we expect?
RWE has been accepted as evidence for medical devices (in the US) and in Europe for drugs, but only recently has the FDA released the RWE Framework that will pave the way for the use of RWE to gain approval for pharmaceuticals in the US.
The Process to Receive Approval for Market Entry
In order for a new product to receive approval for market entry, evidence from randomized clinical trials (RCT) must be submitted to the local regulatory body to ensure that the product is safe, effective and necessary for use by patients. If a product is already commercially available in one country, and the company wants to revise the labeling or enter a new market, does the company still need to provide the justification from an RCT? Or, can the manufacturer leverage evidence that has already been collected and is just sitting there, waiting to be analyzed? Clinical trials can be long, expensive and not representative of the general population – leaving opportunity and reason to use RWE in a complementary fashion. Here are two examples:
In 2011, the FDA approved a novel treatment for trans-catheter aortic valve replacement (TAVR). The organization receiving the approval collected Real World Data (RWD) from a registry database and was able to analyze the off-label use of the procedure. Since enough supporting evidence was collected on the off-label use, the company was able to receive additional approval for a new treatment using the results from the RWE study. (1)
Roche received FDA approval to market a lung cancer therapy in the US but received conditional approval in the EU and was required to provide additional evidence towards the efficacy of the product. In order to meet these obligations, Roche worked with Flatiron Health to provide evidence through RWD in addition to conducting a Phase III RCT. The RWE portion included a retrospective analysis of electronic health records, which provided enough evidence to gain approval from several European health technology assessments (HTAs) prior to the completion of the Phase III RCT. (2)
Both case studies led to compiling evidence faster, quicker regulatory approval and achieved cost savings – proving RWE has the potential to bring products to patients faster than waiting for evidence from a RCT. That being said, the data source needs to be of high quality. The reason the two use cases above were able to receive approval was due to the completeness of the data. Remember, regulatory bodies will still need to inspect the data for safety, function and improvement of health outcomes. RWE has disadvantages with confounding, while RCT is designed to inhibit confounders in order to prove the treatment is the cause of a beneficial outcome.
Download the exclusive white paper to learn about challenges in HEOR & RWE sourcing.
In short, RWE usage is here and will only continue to grow, especially since the FDA released the new framework and guidance for RWE utilization in the regulatory approval process. This is the biggest reason RWE will grow in the future, followed by the explosion of the data sources. RWE is not meant to replace RCT; RWE is meant to complement RCT or even address the pitfalls of time and cost. Using robust data sources to complement clinical trials will provide superior results for the patient. Leveraging smart study designs, answering important research gaps and working collaboratively with suppliers to conduct RWE studies is a successful strategy in this space.
Shuren, J. & B. Zuckman. (2017) “How Creative FDA Regulation Let to First-in-the-World Approval of a Cutting-Edge Heart Valve.” Available at: https://www.massdevice.com/creative-fda-regulation-led-first-world-approval-cutting-edge-heart-valve/
Chatterjee, A. et al. (2018) “Real-World Evidence: Driving a New Drug Development Paradigm in Oncology.” McKinsey & Company. Available at: https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/real-world-evidence-driving-a-new-drug-development-paradigm-in-oncology
Antibodies have re-shaped biomedical researches since their discovery. From research tools to therapeutics and diagnostics, antibodies are indispensable in finding cures for a host of different diseases. In recent years, antibody-based therapeutics have dramatically changed the way we treat diseases, especially in oncology. The recent introduction of platforms has further advanced how antibodies are being used.
One platform—the SMAbTM— produces with high efficiency, specific, stability and diversity in half the time as other monoclonal antibody development platforms. The innovative, single B-cell antibody culture and screening platform was produced by Yurogen, who specializes in custom rabbit and camelid monoclonal antibody development.
The SMabTM platform produces high-quality antibodies using peripheral blood mononuclear cells (PBMCs) or splenocyte cells from immunized rabbits and camelids. The custom antibodies can then be used to enrich and identify positive clones via various function-based funneling strategies that use the primary B cell supernatant to quickly identify positive clones with desired biological properties, making screening throughput easily scalable and highly customizable according to a researcher’s needs. With cost effectiveness in mind, Yurogen’s efficient mAb screening eliminates repetitive and unnecessary work to save clients time and resources, allowing researchers to get monoclonal antibodies to their antigens in about 18 weeks. A short turnaround time gives researchers an edge in advancing their projects versus competitors.
Over the years, Yurogen has generated antibodies for use in many applications including but not limited to ELISA, Western Blot, Immunofluorescence, Thin layer immunoassay, FACS, Immunohistochemistry and immuno-oncology. Yurogen, however, is more than an antibody development company. It also offers comprehensive antibody services, such as antigen design, custom peptide synthesis and antibody affinity and humanization.
Stem cells have attracted a great deal of deserved attention due to their lineage-independent characteristics. In other words, they have the potential to be differentiated into a countless number of cell types. Adult stem cells, otherwise known as inducible pluripotent stem cells (iPSCs), are particularly favorable as research tools because they are derived from a patient’s somatic cells such as blood, skin or muscle. As such, iPSC models serve as “patient in a dish” models, offering advantages over conventional methods – like rodent models and immortalized cell lines – that are not always able to model human disease or may have numerous genetic and genomic instability problems.
iPSC Models to Improve Efficiency of Drug Discovery and Development
Tempo Bioscience creates patient-derived iPSC models that can be engineered into 3D spheroids and organoid models that provide meaningful results and insights for scientists. The company continues to stay innovative by engineering numerous iPSC models, 3D spheroids and organoid models from a wide range of donors and incorporates Tempo’s biosensor technology that serves as fluorescent intensiometric reporters for recording live-cell responses into the models. The company believes that as the need for iPSC models increases, the field will expand its applications to include additional cell-based disease models, multi-organ toxicity assays, cytotoxicity assays and biomarker validations. In the article, iPSC Models to Improve Efficiency of Drug Discovery and Development, the team from Tempo Bioscience discusses several key issues regarding how the iPSC models can improve the efficiency of drug discovery and development.
To learn more about Tempo Bioscience and their services, visit their profile here.
As a relatively new means of conducting research in the life sciences, RWE, or real-world evidence, is data that comes from “real world settings” such as a clinical practice. Studies driven by real world evidence, or real-world data (RWD), can utilize data from medical records or claims databases,1 be conducted prospectively in observational studies or adhere to a mixed, hybrid-design approach.2 Thus, RWE does not originate from the tightly controlled environment of clinical trials; instead, RWE replicates the same behaviors one would see in a real-world setting or typical clinical practice. In fact, one could say RWE provides essential insights on a range of outcomes that are representative of an everyday clinical setting, while randomized clinical trials provide efficacy and safety and are crucial for product registration.
In the context of drug development, the Phase 1-3 clinical trial phase is where researchers study whether or not a drug is safe, effective and does what it is intended to do–make people better.2 As the clinical trials progress, more patients are added in each phase, more evidence is collected to prove the drug is safe and effective, then the clinical trial data is presented to a regulatory agency and hopefully receives a stamp of approval to be placed on the market. Once this occurs, doctors start prescribing the drug to their patients, which is where the bulk of RWE is produced, as the data on the new drug is recorded in medical and claims records as well as through patient experience surveys. RWE studies are then conducted to answer a variety of questions that were not answered in the clinical trial setting: How do patients actually adhere to the drug regimen? Is the drug prescribed in other indications? What is the real cost of the product to the patient and healthcare system? RWD can also be used to improve future clinical trials by informing researchers of the populations most likely to benefit from product regimen or to identify additional outcomes to assess.
How RWE Works
RWE demonstrates how a product performs in the real world among the general population while taking into consideration factors that could influence the outcome of a disease (e.g. co-morbidities, human behavior, provider treatment patterns). On the other hand, data from clinical trials shows how a product performs under a tightly controlled and closely monitored setting that provides or even favors the best environment for the product to perform successfully and eventually reach the market. RWE studies dictate whether a product is still safe and effective once it does in fact hit the market—a real world setting—and is affected by the aforementioned factors that can influence the natural course of disease and product performance.2 While there is much value to be gained from RWE, there are challenges with analyzing this type of data.
If a researcher is not careful to take certain considerations into account when designing a study, confounders are more likely to be introduced and influence the results.3 Within the general population, people sometimes have more than one disease, so they are prescribed different medications that could interact with each other. Smoking, age and weight are all elements that can potentially affect the outcome. However, this scenario is a more accurate representation of the general population and provides more information on outcomes of the product when these factors are introduced.
With all that being said, clinical trials have been and are still considered the gold standard within research, which is why historically RWE had not received much attention in years past.3 Clinical trials have the distinct benefits of effectively randomizing the product among different treatment groups, minimizing confounders and maintaining causality in studies. However, people are also realizing the benefits of RWE in helping to truly understand the most accurate outcomes of their product. And because of this, regulatory agencies are increasingly asking for more data from RWE studies.
Challenges Associated with RWE
Despite the recent interest in RWE, it does not come without challenges. Firstly, an RWE study must include real world data gleaned from hospital records, patient registries, claims databases or collected prospectively from the clinician or patient. This information is traditionally not easily accessible, as most all countries tightly regulate access to medical records and patient data.3 Not to mention, data quality is an issue because medical records are not designed for research; their main purpose is for a clinical practice to treat patients.3 Another challenge is finding the right data to use for a study that showcases the value of a product, which is only compounded by finding the right data source.
Recently, contract research organizations (CROs), consulting groups, the pharmaceutical industry and even the payer organizations have begun expanding into RWE services. Research organizations are increasingly realizing that in order to conduct successful RWE studies they must seek external partnerships and outsource the work to these vendors with RWE experience. Organizations specializing in RWE services can accelerate access to RWD and provide insight into appropriate study design for specific research questions. Yet, it’s not easy finding the right RWE supplier—visibility into which group owns and can access data is murky at best, and if they do have access to the data, what do they have access to? All of these factors may hinder finding the right data. Analyzing the data and proving the value of a product further slows down time to insight, which is not cost-effective.
Sourcing Simplified: The HEOR & RWE Marketplace
Currently, many researchers not using an online marketplace attempt to find the right RWE supplier through word of mouth such as asking friends, colleagues or academic institutes, among others, creating a sort of spider web of connections that can add several months to a study. The new HEOR & RWE Marketplace, a collaboration between two trusted life science brands, HealthEconomics.Com and Scientist.com, addresses the challenges RWE stakeholders face today by connecting research organizations and RWE service providers all on one platform. The Marketplace makes it easier for organizations to find suppliers who have 1) appropriate data access that research organizations require 2) the expertise to design and implement RWE studies 3) expertise in specific therapeutic areas 4) and an understanding of the data they own as well as its origin. All of these benefits, coupled with the fact that it shortens time to find a qualified supplier, drastically reduces timelines and helps drive time to insight.
For existing Scientist.com users looking to incorporate RWE studies into their current pipeline of projects, this new partnership is expanding our already large supplier network. And if you have preferred suppliers, the Marketplace reduces the time to contract with an award-winning compliance tool that follows the same checks and balances of a client’s internal organization. This framework provides procurement and legal teams more control over the proposals, reducing the time to contract. This can be a huge benefit if a client has a regulatory question that needs a quick response so more time can focus on the quality of the research.
We recognize that there is an increasing need for access to HEOR and real-world data to make faster and more informed healthcare decisions and help guide treatment approaches. The HEOR & RWE Marketplace is an online solution that accelerates the sourcing and procurement process for researchers and suppliers of HEOR/ RWE and market access services. By streamlining the process for buyers and sellers, the Marketplace will deliver reduced time to contract, quicker time to insight and faster market access.
Miksad, R. A., & Abernethy, A. P. (2017). Harnessing the Power of Real-World Evidence (RWE): A Checklist to Ensure Regulatory-Grade Data Quality. Clinical pharmacology and therapeutics, 103(2), 202-205. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814721/
Sherman, R. E., et al. (2016). Real-world evidence: What is it and what can it tell us? The New England Journal of Medicine. 375(23): 2293-2297. Available at: http://buster.zibmt.uni-ulm.de/dien/DPV-Wiss-Real-World%20Evidence%20-%20What%20Is%20It%20and%20What%20Can%20It%20Tell%20Us.pdf
Hampson, G., et al. (2018). Real world evidence for coverage decisions: Opportunities and challenges. A Report from the 2017 ICER Membership Policy Summit. Institute for Clinical and Economic Review. Available at: https://icer-review.org/wp-content/uploads/2018/03/ICER-Real-World-Evidence- White-Paper-03282018.pdf
The Intuitive Chemistry Bias by Satyanarayana Janagani, PhD
Two global forces are at odds today – the push for “greener” processes and the demand for lower prices for prescription drugs and materials. Governments and corporations across the globe are adopting policy initiatives and driving scientific innovations to promote sustainable technologies, resulting in an explosion of discoveries based on both chemical- and biocatalytic transformations.
However, there is a general misconception in the industry that biocatalytic processes supersede chemical processes. This unconscious bias among researchers gave birth to a trend that biocatalysis is the necessary tool that will bring us one step closer to the personalized medicine solution. Meanwhile, some companies are making breakthroughs to show that the foundation of drug discovery still remains in chemical processes.
Stereokem’s Chemistry Pyramid should be used as the new standard for chemists to follow in order to remain environmentally conscious.
With biocatalysis, only a few of the enzymes that speed up the reactions tolerate and allow conversions of nonnatural substrates. This partial promiscuity warrants human engineering of enzymes that are sufficiently general to accept a variety of related substrates, but selective enough to yield single stereoisomers. The design of biocatalysts is complicated by the fact that the catalyzed-reactions ought to be chemo-, regio- and stereoselective. The odds of success further multiply considering the ramifications when enzymes are employed under completely nonaqueous conditions.
While there have been quite a few successful examples of biocatalysis as applied to the commercialization of small molecule drugs and intermediates, the overall sustainability is still debatable owing to the sophistication, operational costs and large amounts of aqueous waste being generated.
At Stereokem, researchers are intuitively chemistry-biased and are attempting to prove that chemical methods supersede enzymatic processes in terms of sophistication, throughput, economic viability and sustainability. The company strives to bring “out of the box,” innovative and at times, under-graduate stereochemical concepts to light for designing cost-effective and sustainable chemical processes to commercialization of chiral small molecule drugs and intermediates.
Well-designed chemistry protocols revolutionize the way materials are manufactured and could prove to be at par with, or even superior to, biocatalysis. For every biocatalytic method developed, Stereokem has been endeavoring to develop an equivalent and often optimized alternative chemistry technology for the commercialization of chiral nonnatural substrates.
Enterprising and driven, Stereokem is on a mission to promote chemistry-bias among the peers using clean and green-chemistry. Their initiative is meant to bring about solidarity and encourage chemists to explore possibilities and instigate creative research to expedite the drug discovery process.
To see a full list of Stereokem’s capabilities and services, visit their storefront on the Scientist.com marketplace.